Search

Chikungunya virus (CHIKV) has received global attention due to the series of large-scale outbreaks in different parts of the world. Many unusual clinical severities including neurological complications and death were reported in recent outbreaks. The mechanism underlying the host immune response to CHIKV in the brain is poorly characterized. In this study, the neuropathogenesis of CHIKV with E1:A226 V mutation was elucidated in 1 week old BALB/c mice. The virus was found to replicate in mice brain with peak titer of 104 on 6th day post infection. Immunohistochemical analysis revealed preferential virus localization in neuronal cells of cerebellum. The expression profiling of TLR, antiviral genes and cytokines in mice brain revealed significant up regulation of TLR3, TRAF-6, TICAM-1, MCP-1, CXCL-10, IL-6, IL-4, ISG-15, MX-2, IFN-β, OAS-3 genes that ultimately resulted in virus clearance from brain by day 9-10 suggesting activation of innate immune pathway. Further the effect of poly I: C (Polyinosinic: Polycytidylic acid), a TLR-3 agonist and potent IFN inducer on CHIKV neuropathogenesis was studied. Pretreatment of mice with Poly I: C caused reduction of CHIKV titer in brain and offered 100% protection of animals. The protection was mediated by an increased induction of TLR3, IFN-β and antiviral genes in mice brain. Our result demonstrates that pre immune stimulation of animals by Poly I: C is effective inhibitor of CHIKV replication and might be a promising prevention agent against this virus. [ABSTRACT FROM AUTHOR]

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved surveillance mechanism across eukaryotes and also regulates the expression of physiological transcripts, thus involved in gene regulation. It essentially ensures recognition and removal of aberrant transcripts. Therefore, the NMD protects the cellular system by restricting the synthesis of truncated proteins, potentially by eliminating the faulty mRNAs. NMD is an evolutionarily conserved surveillance mechanism across eukaryotes and also regulates the expression of physiological transcripts, thus involved in gene regulation as well. Primarily, the NMD machinery scans and differentiates the aberrant and non-aberrant transcripts. A myriad of cellular dysfunctions arise due to production of truncated proteins, so the NMD core proteins, the up-frameshift factors (UPFs) recognizes the faulty mRNAs and further recruits factors resulting in the mRNA degradation. NMD exhibits astounding variability in its ability in regulating cellular mechanisms including both pathological and physiological events. But, the detailed underlying molecular mechanisms in NMD remains blurred and require extensive investigation to gain insights on cellular homeostasis. The complexity in understanding of NMD pathway arises due to the involvement of numerous proteins, molecular interactions and their functioning in different steps of this process. Moreover methods such as alternative splicing generates numerous isoforms of mRNA, so it makes difficulties in understanding the impact of alternative splicing on the efficiency of NMD functioning. Role of NMD in cancer development is very complex. Studies have shown that in some cases cancer cells use NMD pathway as a tool to exploit the NMD mechanism to maintain tumor microenvironment. A greater level of understanding about the intricate mechanism of how tumor used NMD pathway for their benefits, a strategy can be developed for targeting and inhibiting NMD factors involved in pro-tumor activity. There are very little amount of information available about the NMD pathway, how it discriminate mRNAs that are targeted by NMD from those that are not. This review highlights our current understanding of NMD, specifically the regulatory mechanisms and attempts to outline less explored questions that warrant further investigations. Taken as a whole, a detailed molecular understanding of the NMD mechanism could lead to wide-ranging applications for improving cellular homeostasis and paving out strategies in combating pathological disorders leaping forward toward achieving United Nations sustainable development goals (SDG 3: Good health and well-being)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The extracellular matrix (ECM) is a significant component of the brain, constituting up to 20 % of the brain volume and perform multifarious functions during development, maturation and regeneration of the central nervous system (CNS). ECM molecules assemble systematically to form a relatively rigid and unique lattice-like structure, known as perineuronal nets (PNNs). The PNNs usually envelop the cell body and initial axon segment and are characterized by a mesh-like structure extending along dendrites of neurons. PNNs play prominent role in the early neural development, from migration and differentiation to axonal path finding. They regulate plasticity and regeneration in adulthood by surrounding and stabilizing synaptic contacts. In this review, we have focused on the basic structure, distribution and visualization of PNNs and their role during critical periods of development, synaptogenesis and regulation of synaptic plasticity. Furthermore, we have also tried to evaluate the participation of PNNs in the pathophysiology of several brain disorders and their potential in lowering local oxidative stress. Taken together, the concepts outlined in this review emphasize the heterogeneity of PNNs in response to normal physiological and pathological conditions, highlighting the need for future studies on PNNs to target their role in etiology and potential therapeutic interventions in neurological disorders., Competing Interests: Conflict of interests The authors declare no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Incidence of cognitive and emotional alterations are reportedly two times more in diabetic patients than in non-diabetic population with hitherto unexplained causation and mechanism. Purview of the hippocampus functional diversity sanctions the accessibility and the necessity to investigate the regional neuro-immunological aspects of neurodegeneration and related functional alterations following diabetes. We examined the possible involvement of microglia activation, macrophage response, oxidative stress and inflammatory stature in both ventral and dorsal hippocampus of rats rendered diabetic by a single injection of streptozotocin (STZ; 45 mg/ kg body weight; intraperitoneal). Cognitive and behavioural alterations were studied using open field test (locomotor activity), elevated plus maze (anxiety), Barnes maze (spatial cognition) and T maze (working memory) at 2nd, 4th, 6th, 8th, 10th and 12th week post diabetic confirmation. Oxidative stress was investigated via measuring the level of lipid peroxidation biochemically. Scenario of microglia activation, macrophage response and inflammation was gauged using qualitative and quantitative analysis. Pronounced macrophage expression and activation directed microglia phenotypic switching was prominent in both ventral and dorsal hippocampus indicating the impact of oxidative stress following diabetes in hippocampus. The resultant inflammatory response was also progressive and persistent in both ventral and dorsal hippocampus parallel to the altered cognitive, locomotor ability and anxiety behaviour in diabetic rats. Conclusively, present data not only comprehends the microglia, macrophage physiology and related immune response in functionally different hippocampal regions associated cognitive and behavioural deficits, but also offers a suggestive region-specific cellular mechanism pathway for developing an imminent therapeutic approach during particular diabetes deficits., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The age-pigment, lipofuscin that accumulates in cells intrinsically and progressively with age is considered as the hallmark of aging. This accumulation is more prominent in post-mitotic cells like neurons and also appears in glia., Purpose: The aim of the present study was to assess the age-associated occurrence and distribution pattern of lipofuscin both in neurons and microglia in various regions of hippocampus and striate cortex., Methods: The accumulation pattern of lipofuscin in hippocampus and striate cortex was observed in the female Wistar rats of 6 age groups, that is, 3, 6, 12, 18, 24, and 30 months using the autofluorescent property of lipofuscin and its specific localization in neurons and microglia by dual immunolabeling with NeuN and Iba-1 antibodies respectively. Cytoarchitectural and the morphological age-related changes were observed with cresyl violet staining., Results: Lipofuscin pigments accumulate progressively through the normal aging process in hippocampus and striate cortex. However, in hippocampus, lipofuscin accumulates in a region-specific manner with the highest accumulation observed in cornu ammonis (CA) 1 and 3 subregions. Furthermore, the lipofuscin accumulation was also observed in microglia in the senile brains both in the hippocampus and striate cortex., Conclusion: The progressive deposition of lipofuscin could result in cellular dysfunction. This encouraged us to forward the idea that microglia not only participate in the removal of the pigment from the neurons but also accumulate these waste products in itself. Such senescent microglia may contribute to age- related neurodegeneration as they lose the neuroprotective potential due to oxidative stress and thus may be unable to effectively phagocytose the age pigment.

Background: Neonatal bacterial infections have been reported to cause white matter loss, although studies concerning the influence of infection on the expression of myelin and aging are still in their emerging state., Purpose: The present study aimed to investigate the effects of perinatal lipopolysaccharide (LPS) exposure on the myelination at different age points using histochemical and immunocytochemical techniques and the relative motor coordination., Methods: A rat bacterial infection model was established by exposing the neonatal rats with LPS (0.3 mg/kg body weight, i.p., on postnatal day (PND) 3 followed by a booster at PND 5) and its impact was studied on the myelination and motor coordination in young, adult, and senile rats., Results: The results obtained suggest that the administration of LPS induces demyelination, predominantly in cortex and corpus callosum. Low expression level of myelin oligodendrocyte glycoprotein (MOG) was observed at all time points, with prominence at 12, 18, and 24 months of age. In addition, reduced staining with luxol fast blue stain was also recorded in the experimentals. With the increasing demyelination and declining motor ability, LPS exposure also seemed to accelerate normal aging symptoms., Conclusion: There is a direct correlation of myelin damage and poor motor coordination with age. This would provide a better incite to understand inflammation-associated demyelinating changes in age-associated neurodegenerative disorders. Since, no long-term studies on behavioral impairments caused by LPS-induced demyelination in the central nervous system has been reported so far, this work would help in the better understanding of the long-term pathological effects of bacterial-induced demyelination.

Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Tuberculosis and cryptococcal infection of the central nervous system are common AIDS-associated opportunistic infections in tropical underdeveloped and developing countries. To date, research on these infections has focused on clinical, imaging, laboratory diagnosis, and animal models to elucidate the pathogenesis. There is paucity of information on astroglial and microglial alterations in the human nervous system following these infections., Methodology: The pathomorphologic and morphometric alterations of astroglia and microglia in the prefrontal cortex and hippocampus in cases of tuberculous meningitis (TBM) and cryptococcal meningitis (CM) with and without associated HIV were described and compared with cases of HIV encephalitis without opportunistic infections (OI) and HIV-negative human brain tissue., Results: In TBM, the microglia and astrocytes were activated with hypertrophy and hyperplasia, aggregating in the subpial zone and around granulomas in meningeal exudate. In cases of cryptococcal meningitis, reactive changes were less prominent, though activation of both cellular elements was found. Association of HIV with these OIs resulted in muted glial and microglial response. In HIV encephalitis without OI, the level of activation of was low. Both astroglial and microglial cells expressed caspase-3, a pro-apoptotic marker, following HIV and opportunistic infections. Neuronal apoptosis, a mechanism to ensure neuronal survival, was less evident. The reactive astrocytes and microglia following opportunistic infection developed dystrophic changes heralding senescence., Conclusions: Further studies on neuronal-astroglial-microglial interaction will offer deeper insight into the pathogenetic and immune mechanisms in the cellular and pathomorphological evolution of tuberculous and cryptococcal infections.

Behavioral impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45 mg/kg body weight; intraperitoneally). Motor function alterations were studied using Rotarod test (motor coordination) and grip strength (muscle activity) at 2nd, 4th, 6th, 8th, 10th, and 12th week post-diabetic confirmation. Scenario of glial (astroglia and microglia) activation, cell death and glutamate transportation was gaged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labeling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioral alterations following STZ-induced diabetes.

Diabetes Mellitus is associated with increased risk of cognitive and behavioural disorders with hitherto undeciphered role of glia. Glia as majority population in brain serve several vital functions, thus require pertinent revelation to further explicate the mechanisms affecting the brain function following diabetes. In this study we have evaluated glial changes in terms of phenotypic switching, proliferation and expression of activation cell surface markers and associated cellular degeneration in hippocampus following STZ-induced diabetes and caused cognitive impairments. Experimental diabetes was induced in Wistar rats by a single dose of STZ (45 mg/kg body weight; intraperitoneally) and changes were studied in 2nd, 4th and 6th week post diabetes confirmation using Barnes maze and T-maze test, immunohistochemistry and image analysis. An increase in GFAP expression sequentially from 2nd to 6th weeks of diabetes was analogous with the phenotypic changes and increased astrocyte number. Elevated level of S100β with defined stellate morphology further confirmed the astrocytosis following diabetes. Enhanced level of Iba-1 and MHC-II revealed the corroborated microglial activation and proliferation following diabetes, which was unresolved till date. Increased caspase-3 activity induced profound cell death upto 6th weeks post diabetes confirmation. Such caspase 3 mediated cellular damage with a concomitant activation of the astrocytes and microglia suggests that diabetes linked cell death activates the astrocytes and microglia in hippocampus which further underpin the progression and severity of brain disorders resulting in cognitive and behavioural impairments.

Chikungunya virus (CHIKV) has received global attention due to the series of large-scale outbreaks in different parts of the world including Africa, Indian Ocean Islands, India and South-East Asia. The appearance of many unusual severe manifestations including neurological disorders was reported in post resurgence epidemics with implication of novel East Central South African (ECSA) genotype with E1:A226V mutation. The molecular mechanism of CHIKV neuropathogenesis is not yet understood and very little is known about the host-pathogen interactions. In the present study replication kinetics and innate immune response of ECSA genotype of CHIKV with and without A226V mutation were determined in mouse neuroblastoma cell line (N2a). The 226V mutant strain was more replication competent in N2a cells with a peak titer of 10(8)PFU/ml compared to 10(6)PFU/ml for A226 virus. Besides, the 226V mutant virus showed relatively less induction of antiviral genes i.e. IFN-β, OAS-3, MX-2, ISG-15 and Toll like receptors 3 and 7 as compared to non mutant strain (A226). Further pretreatment of N2a cells either with Poly I: C, IFN-β or TNF-α resulted in inhibition of CHIKV replication hence confirming the role of TLR mediated innate immune response in CHIKV pathogenesis. Differential regulation of TLRs and associated down stream antiviral genes might have attributed for increased pathogenesis of the 226V mutant novel ECSA genotype of CHIKV during the recent epidemics., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The Golgi methods have long been used to study the neuronal soma, axons, dendritic arborization and spines. The major concerns of the Golgi method have been its unpredictable nature (inconsistency of impregnation of the stain), time consumed, tissue hardening and clear background, resulting in several modifications to improve the cellular visualization. In the present work we describe a modification of the rapid-Golgi method that takes the benefit of perfusion fixation (with rapid-Golgi solution) then post-fixation in the same fixative for 36 h followed by 36 h impregnation in aqueous AgNO3 followed by vibratomy. This modification is simpler, faster and inexpensive, provides a consistent staining of neurons with good resolution of neuronal soma, dendritic arborization as well as spines with much reduced formation of silver chromate crystals and background in just 3 days.

Polyinosinic:polycytidylic acid (Poly I:C; 5 mg/kg body weight, ip) and lipopolysaccharide (LPS; 0.3 mg/kg body weight, ip) induced microglial and astrocytic activation in Sprague Dawley rats. Higher microglial and astrocytic activities were noticed in Poly I:C infused rats throughout the hippocampus till postnatal day 21 with a comparatively weaker response in LPS group. However, LPS induced inflammation persisted even after postnatal day 21, indicating thereby, that the Poly I:C (viral mimic) produces an acute inflammation, while LPS (bacterial endotoxin) produces chronic inflammation when exposed during early neonatal life.

Reelin is an extracellular matrix molecule that is involved in the normal development of the cerebellar lamination, Bergmann glial fibres alignment, Purkinje cell monolayer arrangement and granule cell migration. In this study, we have examined the effects of maternal exposure of deltamethrin (DLT), a type II pyrethroid insecticide, on the structural and functional development of rat cerebellum during postnatal life. DLT (0.75 mg/kg body weight, intraperitoneally dissolved in dimethylsulphoxide) was administered in timed pregnant rats during two different gestational time periods, i.e. gestational days of 7-10 and 11-14, respectively. In DLT exposed rats, a significant overexpression of reelin was observed in the cells of the external granule cell layer (EGL) and internal granule cell layer along with an ectopic expression of reelin in the EGL as well as in the migrating granule cells just below the EGL, revealing an arrest of granule cell migration in this zone. Mis-orientation and hypertrophy of the Bergmann glial fibres further hampered the journey of the granule cells to their final destination. Possibly reelin overexpression also caused misalignment of the Purkinje cells and inhibited the neurite growth leading to a significant decrease in the spine density, main dendritic length and width of the dendritic arbour. Thus, it is proposed that the DLT exerts its neurotoxic effects possibly via the intracellular accumulation and low release of reelin leading to an impaired granule cell and Purkinje cell migration, inhibition of neurite outgrowth and reduced spine density. Such impaired cerebellar development leads to motor coordination deficits.

The present study was conducted to correlate rotenone-induced neurotoxicity with cellular and molecular modifications in neuronal and neuronal supportive cells in rat brain regions. Rotenone was administered (3, 6 and 12 μg/μl) intranigrally in adult male Sprague-Dawley rats. After the 7th day of rotenone treatment, specific protein markers for neuronal cells - tyrosine hydroxylase (TH), astroglial cells - glial fibrillary acidic protein (GFAP), microglial cells - CD11b/c, and Iba-1 were evaluated by immunoblotting and immunofluorescence in the striatum (STR) and mid brain (MB). Apoptotic cell death was assessed by caspase-3 gene expression. Higher doses of rotenone significantly lowered TH protein levels and elevated Iba-1 levels in MB. All the doses of rotenone significantly increased GFAP and CD11b/c protein in the MB. In STR, rotenone elevated GFAP levels but did not affect TH, CD11b/c and Iba-1 protein levels. Caspase-3 expression was increased significantly by all the doses of rotenone in MB but in STR only by higher doses (6 and 12 μg). It may be suggested that astroglial activation and apoptosis play an important role in rotenone-induced neurotoxicity. MB appeared as more sensitive than STR toward rotenone-induced cell toxicity. The astroglial cells emerged as more susceptible than neuronal and microglial cells to rotenone in STR., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Chikungunya infection is characterized by fever, rash and arthritis. The disease pathogenesis is still poorly understood. Hence, unveiling the molecular mechanisms that govern the survival and death of neuronal cells infected by Chikungunya virus (CHIKV) was the particular interest of this study. Human neuroblastoma SH-SY5Y cells infected with CHIKV showed characteristic features of apoptosis with activation of caspase-3, cleavage of PARP and translocation of Cyt-c. Cells also showed a loss in the intracellular level of GSH and an increase in the lipid peroxidation of the infected cells with the increasing time of infection, which indicated the involvement of oxidative stress in Chikungunya infection. There was observed a gradual decrease in the fold change of antioxidant enzymes and an increase in the fold change of pro-inflammatory cytokines. This study suggested the implication of virus induced apoptosis in disease pathogenesis which may give a fresh insight for CHIKV induced neuronal cell damage and antiviral therapeutics., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Spirulina platensis treatment (400 mg kg(-1) for 25 days) effectively suppressed peripheral sensitization via modulation of glial activation and improved motor coordination and restoration of functional motor activity in collagen-induced arthritic rats. Spirulina treatment also resulted in an appreciable reduction of the NF200 accumulation in the spinal cord neurons of arthritic rats. This is indicative of neuroprotective action of S. platensis against glutamate excitotoxicity-induced central sensitization produced by the peripheral joint inflammation in the collagen-induced arthritis. The results suggest that effects of S. platensis may be due to its counter regulation of spinal glial activation and could be a potential strategy for the treatment of arthritis.

Rotenone induces neurotoxicity but its correlation with biochemical and cerebral changes in rat brain regions are not well defined. In the present study rotenone was administered (3, 6 and12mug/mul) intranigrally in adult male SD rats and its effect was assessed on neuromuscular coordination and in different brain areas viz. striatum (STR), mid-brain (MB), frontal cortex (FC) and hippocampus (HP) cerebral and biochemical changes on 1st and 7th day after treatment. All the doses of rotenone significantly impaired neuromuscular coordination performance on Rota rod test on 1st and 7th day. TTC staining showed significant increase in cerebral injury volume on 1st and 7th day after rotenone treatment indicating mitochondrial enzyme deficiency but increase after 7th day was less that after 1st day. Rotenone treated rats showed significant decrease in GSH and increase in MDA in different brain regions though the pattern was varied. After 1 day of rotenone (6 and 12mug) treatment significant decrease in GSH was observed in STR and MB while MDA was significantly increased only in MB. The maximal effect on GSH and MDA was obtained in STR and MB on 7th day after treatment with 12mug dose of rotenone. Thus, based on the occurrence of changes, it may be suggested that impairment of neuromuscular coordination is inked to oxidative stress rather than mitochondrial enzyme deficiency, all the processes are correlated with each other with the progression of time. MB appeared as most sensitive brain area towards rotenone toxicity., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Polyinosinic:polycytidic acid (poly I:C) is a synthetic double stranded RNA, which mimics with viral genome and mediates immune activation response similar to double stranded RNA virus infection into the brain. Microglial cells are the immune competent cells of the central nervous system having Toll like receptors-3 on their surface. Upon establishing that poly I:C infusion into the brain causes microgliosis by creating a viral infection model, the present study was designed to evaluate the effects of microglial activation following poly I:C infusion on motor activity. We infused 100 microl of 1% solution of Poly I:C in TBE buffer directly into the lateral ventricle and TBE buffer as vehicle to controls. A significantly higher microglial cell count as compared to control on 2, 3 and 7 days post infusion was recorded. Motor activity and microglial cell count was assessed in both controls and poly I:C infused rats on 1, 2, 3, 7, 14, 21 and 28 days post infusion. A significant decrease in motor activity and motor coordination occurred with respect to control. The results clearly demonstrate that microglial activation has a direct relevance with decreased motor activity. Findings could also have their importance in understanding the role of microglial cells on behavioral aspects in viral diseases.

The presence of microglia in dorsal root ganglia (DRG) has not been reported earlier. The dorsal root ganglia contain satellite glial cells (SGCs) and macrophages, which are considered to have infiltrated from the systemic blood. An attempt was made to investigate whether microglia as found in the central nervous system are also present in the dorsal root ganglia of untreated rats and following experimental peripheral nerve injury. Female adult Wistar rats were subjected to sciatic nerve transection injury on the right hand side. The DRGs of the right side were studied with the contralateral DRGs of the left side serving as controls. The tissues, harvested at different time points after injury, following intracardial perfusion fixation, and frozen sections were immunolabeled with anti-GFAP as a marker for SGCs and anti-Iba1 and OX-6 as markers for microglia and activated macrophagic microglia, respectively. These antibodies were also used in combination to ascertain if Iba1+ cells are the SGCs or otherwise and also if macrophagic OX-6+ cells are Iba1 positive microglia. The results indicate that Iba1 positive microglial cells are different from the SGCs in the DRGs. The Iba1 positive microglial cells respond to the sciatic nerve injury becoming activated and macrophagic and express MHCII molecules. Such activated microglia apparently may serve as neurosupportive cells, providing neuroprotection and scavenging cellular debris in response to the injury.

Aim: To assess the protective efficacy of Spirulina platensis against collagen-induced arthritis (CIA) in female Wistar rats based on the changes in paws thickness, serum albumin, cholesterol, lipid peroxidation, alkaline phosphatase and acid phosphatase activities and histology of paw joints., Methods: Arthritis was induced by intradermal injection of Collagen and Freund's adjuvant incomplete suspension at several sites on the back with a dose of 2 mg kg(-1) of body weight and boosted with 0.1 ml intradermally at the base of the tail. CIA rats were orally treated with 200 and 400 mg kg(-1) per oral of S. platensis from 0 to 45th day., Results: S. platensis at 400 mg kg(-1) per oral significantly elevates serum albumin and decreases the serum cholesterol, alkaline phosphatase and acid phosphatase activities, lipid peroxidation, paw thickness as well as normalize the joint histopathology of CIA rats., Conclusions: S. platensis (400 mg kg(-1)) significantly normalizes changes observed in arthritic rats to near normal conditions, indicates that S. platensis has promising protective efficacy against CIA rats.

In this study, we have evaluated neuroprotective effect of an immunosuppressant immunophilin ligand, FK506, in the sciatic nerve injury model in rats. FK506 was injected to the sciatic nerve transected 3-month-old female Wistar rats (2 mg/kg/day starting 1 day prior to sciatic nerve injury up to 7 day post operation). Equal number of sciatic nerve transected animals served as injured untreated controls. The contralateral side served as respective control. L4-L5 region of the spinal cord was removed on day 1, 3, 7, 14, 21, and 28, post operation and then processed for cryo-sectioning and paraffin sectioning. The cryocut sections were used for immunohistochemistry for localizing all microglia (using anti-Iba-1) and MHC-II expressing microglia (with OX-6). The physical dissector method was applied on Nissl stained paraffin sections for absolute motor neuron counting in the L4-L5 region of spinal cord. FK506 treated animals presented 88.7% neuronal survival while the injured alone had 79.12%, which is significantly less than the treated animals. FK506 caused early proliferation of microglia at 1 and 3 days post operation. FK506 also significantly restricted transformation of these cells in to phagocytes. Colocalization of activated microglia by anti-Iba-1 and OX-6 antibodies, confirms that the MHC-II expressing cells in injured spinal cord are none other than microglial cells and MHC-II expressing cells are significantly less in treated as compared to untreated injured animals. We propose that immunosuppression is one of the main mechanisms by which FK506 protects the central neurons following peripheral injury.

Calcium plays an important role in the pathophysiology of pain. A number of studies have investigated the effect of L-type calcium channel blockers on the analgesic response of morphine. However, the results are conflicting. In the present study, the antinociceptive effect of morphine (2.5 microg) and nimodipine (1 microg) co-administered intraspinally in mice was observed using the tail flick test. It was compared to the analgesic effect of these drugs (morphine - 250 microg subcutaneously; nimodipine - 100 microg intraperitoneally) after systemic administration. Nimodipine is highly lipophilic and readily crosses the blood brain barrier. Addition of nimodipine to morphine potentiated the analgesic response of the latter when administered through the intraspinal route but not when administered through systemic route. It may be due to direct inhibitory effect of morphine and nimodipine on neurons of superficial laminae of the spinal cord after binding to mu -opioid receptors and L-type calcium channels respectively.

Deltamethrin (DLT; 0.7mg/kg/body wt/day, i.p., dissolved in propylene glycol) administration during postnatal days 913 in Albino rat pups, resulted in a delayed appearance of radial glial fibers, that guide the migration of granule cells. Moreover, the radial glial fibers in the DLT-treated pups were disorganized, hypertrophied and heavily stained. Thus, it is being proposed that although after exposure to DLT the neuronal proliferation occurs at normal rate, the neuronal migration along the stumpy and crumpled radial fibers hamper the journey of the healthy neurons to their proper destination.

A study was undertaken on the age-associated histochemical changes in the ventricular myocardium and the influence of meclophenoxate hydrochloride (MPH) on the age pigment lipofuscin. Sixty Wistar albino rats in three age-groups (3, 15 and 30 months old) were treated with meclophenoxate hydrochloride (100 mg/kg body wt/day, ip) for a period of 2-8 wk. Five animals each from the three age-groups served as controls. Various histochemical and micromorphometric studies were carried out on the myocardial tissue. A linear increase in the myocardial volume occupied by the pigment was observed with advancing age. As a result of meclophenoxate treatment, a gradual decrease in the myocardial volume occupied by the pigment was noted. After 4-6 wk treatment, the pigment bodies were found lodged into the capillary endothelium and the lumen, facilitating the removal of the pigment via blood stream. Histochemical and micromorphometric analyses of ventricular myocardium of albino rats have shown thus that deposition of the age-pigment, lipofuscin, can be accepted as an index of cellular ageing.

This paper deals with some deleterious effects of protein malnourishment in rat cerebellum. Severe protein deprivation enhanced the formation of 'dark' cells in white rats. It is postulated that abnormal changes in the neuronal contents induced by nutritional stress play a vital role in the formation of the 'dark' cells through an intermediary stage, 'semi-dark' cells. Centrophenoxine a lipofuscinolytic agent, however, seems to interfere with the process of formation of 'dark' cells and/or helps reconversion of the 'dark' cells into the normal or 'light' type Purkinje cells.

Senile white rats were treated with centrophenoxine at a dosage of 100 mg/Kg body weight/day for 60 days intraperitoneally. Sections of variously fixed and embedded cerebella were studied cytochemically to note the effect of the drug on the senile Purkinje neurons. The nucleolus was found to be hyper-active, as evidenced by the processes of budding and extrusion. A frank regeneration of the Nissl patches along with an increase in alpha-esterase and decrease in the activity of acid phosphatase and simple esterase was noted in the Purkinje cells after 60 days' treatment. It is suggested that the drug exerts its positive effects by regenerating the general cytoplasm and by revitalizing the nucleocytoplasmic interactions in the senile Purkinje cells.