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Contrasting to tetrahydrocannabinol (THC), cannabidiol (CBD) has virtually no psychoactive effects and thus presents a minor risk for abuse. Furthermore, emerging preclinical and clinical evidence indicates that CBD exerts several beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. Even though fever is one of the responses associated with systemic inflammation, no previous study assessed the putative impact of CBD on lipopolysaccharide (LPS)-induced fever. The present study aimed to evaluate whether CBD exerts effects on febrile responses, by modulating the hypothalamic-pituitary-adrenal (HPA) axis, and the inflammatory reflex, in this response. CBD caused no change in euthermic mice, indicating that it does not alter euthermia. Conversely, CBD blunted all the assessed systemic inflammation parameters including fever (a hallmark of infection), plasma pro-inflammatory cytokines and prostaglandin E 2 (PGE 2 ) surges, and hypothalamic PGE 2 (the proximal mediator of fever) synthesis. Moreover, CBD also reduced LPS-induced increase in plasma corticosterone levels and spleen TNF-α. These data are consistent with the notion that CBD has antipyretic effects, reducing peripheral febrigenic signaling (plasma pro-inflammatory cytokines levels), and eventually down-modulating hypothalamic PGE 2 production, possibly in a corticosterone- and inflammatory reflex-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We notify that there's no financial/personal interest or belief that could affect our objectivity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We tested the efficacy of 4'-fluorocannabidiol (4'-F-CBD), a semisynthetic cannabidiol derivative, and HU-910, a cannabinoid receptor 2 (CB2) agonist in resolving l-DOPA-induced dyskinesia (LID). Specifically, we were interested in studying whether these compounds could restrain striatal inflammatory responses and rescue glutamatergic disturbances characteristic of the dyskinetic state. C57BL/6 mice were rendered hemiparkinsonian by unilateral striatal lesioning with 6-OHDA. Abnormal involuntary movements were then induced by repeated i.p. injections of l-DOPA + benserazide. After LID was installed, the effects of a 3-day treatment with 4'-F-CBD or HU-910 in combination or not with the TRPV1 antagonist capsazepine (CPZ) or CB2 agonists HU-308 and JWH015 were assessed. Immunostaining was conducted to investigate the impacts of 4'-F-CBD and HU-910 (with CPZ) on inflammation and glutamatergic synapses. Our results showed that the combination of 4'-F-CBD + CPZ, but not when administered alone, decreased LID. Neither HU-910 alone nor HU-910+CPZ were effective. The CB2 agonists HU-308 and JWH015 were also ineffective in decreasing LID. Both combination treatments efficiently reduced microglial and astrocyte activation in the dorsal striatum of dyskinetic mice. However, only 4'-F-CBD + CPZ normalized the density of glutamate vesicular transporter-1 (vGluT1) puncta colocalized with the postsynaptic density marker PSD95. These findings suggest that 4'-F-CBD + CPZ normalizes dysregulated cortico-striatal glutamatergic inputs, which could be involved in their anti-dyskinetic effects. Although it is not possible to rule out the involvement of anti-inflammatory mechanisms, the decrease in striatal neuroinflammation markers by 4'-F-CBD and HU-910 without an associated reduction in LID indicates that they are insufficient per se to prevent LID manifestations., Competing Interests: Declaration of competing interest Francisco S. Guimarães is a co-inventor of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL 2014/050023″ Def. US no. Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927). The University of São Paulo has licensed the patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of São Paulo has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a pharmaceutical product containing synthetic cannabidiol and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson's disease, and anxiety disorders.” The other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Trigeminal neuralgia (TN) is an intense and debilitating orofacial pain. The gold standard treatment for TN is carbamazepine. This antiepileptic drug provides pain relief with limited efficacy and side effects. To study the antinociceptive potential of cannabidiol (CBD) and its fluorinated analog PECS-101 (former HUF-101), we induced unilateral chronic constriction injury of the infraorbital nerve (IoN-CCI) in male Wistar rats. Seven days of treatment with CBD (30 mg/kg), PECS-101 (3, 10, and 30 mg/kg), or carbamazepine (10 and 30 mg/kg) reduced allodynia and hyperalgesia responses. Unlike carbamazepine, CBD and PECS-101 did not impair motor activity. The relief of the hypersensitive reactions has been associated with transient receptor potential vanilloid type 1 (TRPV1) modulation in the trigeminal spinal nucleus. CBD (30 mg/kg) and PECS-101 (10 and 30 mg/kg) reversed the increased expression of TRPV1 induced by IoN-CCI in this nucleus. Using a pharmacological strategy, the combination of the selective TRPV1 antagonist (capsazepine-CPZ - 5 mg/kg) with sub-effective doses of CBD (3 and 10 mg/kg) is also able to reverse the IoN-CCI-induced allodynia and hyperalgesia responses. This effect was accompanied by reduced TRPV1 protein expression in the trigeminal spinal nucleus. Our results suggest that CBD and PECS-101 may benefit trigeminal neuralgia without motor coordination impairments. PECS-101 is more potent against the hypernociceptive and motor impairment induced by TN compared to CBD and carbamazepine. The antinociceptive effect of these cannabinoids is partially mediated by TRPV1 receptors in the caudal part of the trigeminal spinal nucleus, the first central station of orofacial pain processing., Competing Interests: Declaration of competing interest Francisco S. Guimarães is a co-inventor of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023” Def. US no. Reg. 62,193,296; 29/07/2015; INPI on 19/08/2015 (BR1120150164927). The University of São Paulo has licensed the patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of São Paulo has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a pharmaceutical product containing synthetic cannabidiol and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson's disease, and anxiety disorders.” The other authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Few pharmacological treatments are available for substance use disorders (SUDs). Neuroplastic changes induced by increased activity of metalloproteinase (MMP) enzymes in the brain are among the several molecular processes that may play a role in drug addiction. Doxycycline, a widely used tetracycline that crosses the blood-brain barrier, inhibits MMPs and has been investigated as a potential treatment for brain disorders. However, the effects of doxycycline on rewarding properties of drugs of abuse remain not investigated. Here, we tested the effects of low doses of doxycycline on the rewarding effects of morphine and cocaine in conditioned place preference (CPP) and locomotor sensitization in mice. Acute doxycycline (10 mg/kg) attenuated the cocaine-induced CPP and hyperlocomotion. Repeated doxycycline (10 mg/kg) blocked hyperlocomotion and attenuated the locomotor sensitization induced by cocaine. It also decreased the rewarding effects in the CPP induced by morphine and cocaine. Our results suggest that doxycycline could be repurposed for treating SUDs., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Despite attenuating the positive symptoms, drugs currently used to treat schizophrenia frequently do not improve the negative symptoms and cognitive impairments. In addition, they show low tolerability, which has been associated with high rates of treatment discontinuation. Recent evidence suggests that the endocannabinoid system may be a target for schizophrenia treatment. The CB2 receptor modulates dopaminergic neurotransmission, which is abnormally enhanced in schizophrenia patients. Here, we aimed to evaluate whether HU-910, a selective CB2 receptor agonist, would reverse schizophrenia-related behavioral changes observed after the acute injections of amphetamine or the N-methyl-d-aspartate receptor (NMDAR) antagonist MK-801. We also investigated the effects of HU-910 in the memory impairment caused by repeated MK-801 administration. Finally, we tested whether HU-910 would produce the cannabinoid tetrad (catalepsy, hypolocomotion, hypothermia, and antinociception). In male C57BL/6 mice, the acute treatment with HU-910 (30 mg/kg) prevented the hyperlocomotion induced by acute MK-801. This effect was blocked by the CB2 receptor antagonist AM630 (1 mg/kg). On the contrary, HU-910 did not prevent the increased locomotor activity caused by acute amphetamine. The acute treatment with HU-910 (3, 10, and 30 mg/kg) also attenuated the impairments in the prepulse inhibition test induced by acute MK-801 and amphetamine. The repeated treatment with HU-910 attenuated the cognitive impairment caused by chronic administration of MK-801 in the novel object recognition test. Furthermore, HU-910 did not produce the cannabinoid tetrad. These results indicate that HU-910 produced antipsychotic-like effects and support further research on the potential therapeutic properties of this compound to treat schizophrenia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cannabidiol (CBD), a major non-psychotomimetic component of the Cannabis sativa plant, shows therapeutic potential in several psychiatric disorders, including schizophrenia. The molecular mechanisms underlying the antipsychotic-like effects of CBD are not fully understood. Schizophrenia and antipsychotic treatment can modulate DNA methylation in the blood and brain, resulting in altered expression of diverse genes associated with this complex disorder. However, to date, the possible involvement of DNA methylation in the antipsychotic-like effects of CBD has not been investigated. Therefore, this study aimed at evaluating in mice submitted to the prepulse inhibition (PPI) model: i) the effects of a single injection of CBD or clozapine followed by AMPH or MK-801 on PPI and global DNA methylation changes in the ventral striatum and prefrontal cortex (PFC); and ii). if the acute antipsychotic-like effects of CBD would last for 24-h. AMPH (5 mg/kg) and MK-801 (0.5 mg/kg) impaired PPI. CBD (30 and 60 mg/kg), similar to clozapine (5 mg/kg), attenuated AMPH- and MK801-induced PPI disruption. AMPH, but not MK-801, increased global DNA methylation in the ventral striatum, an effect prevented by CBD. CBD and clozapine increased, by themselves, DNA methylation in the prefrontal cortex. The acute effects of CBD (30 or 60 mg/kg) on the PPI impairment induced by AMPH or MK-801 was also detectable 24 h later. Altogether, the results show that CBD induces acute antipsychotic-like effects that last for 24-h. It also modulates DNA methylation in the ventral striatum, suggesting a new potential mechanism for its antipsychotic-like effects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The musculoskeletal orofacial pain is a complex symptom of Parkinson's disease (PD) resulting in stomatognathic system dysfunctions aggravated by the disease rigidity and postural instability. We tested the effect of cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, in PD-related myofascial pain. Wistar adult female and male rats orofacial allodynic and hyperalgesic responses were tested by Von Frey and formalin tests, before and 21 days past 6-OHDA lesion. Algesic response was tested after masseter muscle injection of CBD (10, 50, 100 μg in 10 μL) or vehicle. Males compared to females in all estrous cycles' phases presented reduced orofacial allodynia and hyperalgesia. According to the estrous cycle's phases, females presented distinct orofacial nociceptive responses, being the estrus phase well-chosen for nociceptive analysis after 6-OHDA lesion (phase with fewer hormone alterations and adequate length). Dopaminergic neuron lesion decreased mechanical and inflammatory nociceptive thresholds in females and males in a higher proportion in females. CBD local treatment reduced the increased orofacial allodynia and hyperalgesia, in males and females. The female rats were more sensitive to CBD effect considering allodynia, responding to the lowest dose. Although females and males respond to the effect of three doses of CBD in the formalin test, males showed a superior reduction in the hyperalgesic response. These results indicate that hemiparkinsonian female in the estrus phase and male answer differently to the different doses of CBD therapy and nociceptive tests. CBD therapy is effective for parkinsonism-induced orofacial nociception., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD. Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pharmacological manipulation of nitric oxide (NO) has been suggested as a promising treatment for schizophrenia symptoms. A single infusion of sodium nitroprusside, a NO donor with short half-life, was found to improve schizophrenia symptoms. However, an increasing number of preclinical studies have demonstrated the potential beneficial effects of both NO donors and inhibitors. We investigated the potential synergistic effect of sub-effective doses of the NO donor sodium nitroprusside or the NO inhibitor 7-Nitroindazole (7NI) combined with clozapine, a standard atypical antipsychotic, on counteracting amphetamine or MK-801-induced psychosis-like behaviors. The impact of sodium nitroprusside and 7NI on cAMP regulation in the prefrontal cortex and striatum was also evaluated. Confirming previous results, we found that both NO donors and inhibitors prevented amphetamine-induced effects (prepulse inhibition [PPI] disruption and hyperlocomotion). In addition, we observed a synergistic effect of sodium nitroprusside and clozapine on antagonizing the disruptive effects of amphetamine, but not MK-801, in the PPI test. The sub-effective dose of 7NI tested did not prevent amphetamine or MK-induced PPI effects when combined with clozapine. Interestingly, cAMP levels were significantly decreased in the prefrontal cortex after treatment with sodium nitroprusside. In the striatum, both sodium nitroprusside and 7NI blocked the amphetamine-induced increase of cAMP. Our data corroborate previous findings on the dopaminergic mechanisms involved in the action of sodium nitroprusside. It is likely that the differential effects of sodium nitroprusside are related to its ability to modify cAMP levels in the prefrontal cortex., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neurodegenerative diseases are chronic and progressive disorders that affect specific regions of the brain, causing gradual disability and suffering that results in a complete inability of patients to perform daily functions. Amyloid aggregation of specific proteins is the most common biological event that is responsible for neuronal death and neurodegeneration in various neurodegenerative diseases. Therapeutic agents capable of interfering with the abnormal aggregation are required, but traditional drug discovery has fallen short. The exploration of new uses for approved drugs provides a useful alternative to fill the gap between the increasing incidence of neurodegenerative diseases and the long-term assessment of classical drug discovery technologies. Drug re-profiling is currently the quickest possible transition from bench to bedside. In this way, experimental evidence shows that some antibiotic compounds exert neuroprotective action through anti-aggregating activity on disease-associated proteins. The finding that many antibiotics can cross the blood-brain barrier and have been used for several decades without serious toxic effects makes them excellent candidates for therapeutic switching towards neurological disorders. The present review is, to our knowledge, the first extensive evaluation and analysis of the anti-amyloidogenic effect of different antibiotics on well-known disease-associated proteins. In addition, we propose a common structural signature derived from the antiaggregant antibiotic molecules that could be relevant to rational drug discovery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Parkinson's disease is a progressive neurodegenerative disorder characterized by the degeneration of midbrain nigral dopaminergic neurons. Although its etiology remains unknown, the pathological role of several factors has been highlighted, namely oxidative stress, neuroinflammation, protein misfolding, and mitochondrial dysfunction, in addition to genetic predispositions. The current therapy is mainly symptomatic with l-DOPA aiming to replace dopamine. Novel therapeutic approaches are being investigated with the intention of influencing pathways leading to neuronal death and dysfunction. The present review summarizes three novel approaches, the use of which is promising in pre-clinical studies. Polyphenols have been shown to possess neuroprotective properties on account of their well-established antioxidative and anti-inflammatory actions but also due to their influence on protein misfolding and mitochondrial homeostasis. Within the amazing ancillary effects of antibiotics, their neuroprotective properties against neurodegenerative and neuroinflammatory processes are of great interest for the development of effective therapies against Parkinson's disease. Experimental evidence supports the potential of antibiotics as neuroprotective agents, being useful not only to prevent the formation of toxic α-synuclein oligomers but also to ameliorate mitochondrial dysfunction and neuroinflammation. Neuropeptides offer another approach with their diverse effects in the nervous system. Among them, pituitary adenylate cyclase-activating polypeptide, a member of the secretin/glucagon superfamily, has several advantageous effects in models of neurodegeneration, namely anti-apoptotic, anti-inflammatory and antioxidant actions, the combination of which offers a potent protective effect in dopaminergic neurons. Owing to their pleiotropic modes of action, these novel therapeutic candidates have potential in tackling the multidimensional features of Parkinson's disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

It is well known that nitric oxide (NO) interacts with dopamine (DA) within the striatal circuitry. The anti-dyskinetic properties of NO synthase (NOS) inhibitors demonstrate the importance of NO in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID). Here, we investigated the ability of a daily co-treatment of the preferential neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI, 30 mg/kg), with L-DOPA (30 mg/kg) to counteract LID in unilaterally 6-OHDA-lesioned rats. We analyzed striatal nNOS-expressing interneurons, DA and 5-HT neurochemistry in the striatum and alterations of the Fos-B/ΔFosB expression in the corticostriatal, nigrostriatal and mesolimbic pathways. Prolonged administration of 7-NI inhibited the manifestation of chronic L-DOPA treatment-induced abnormal involuntary movements (AIMs). LID was associated with an up-regulation in the number of nNOS-expressing interneurons in the lateral but not medial striatum. nNOS inhibition reduced the number of nNOS-expressing interneurons. The anti-dyskinetic effects of 7-NI correlated with a reduction in DA and 5-HT turnover in the striatum. At postsynaptic striatal sites, 7-NI prevented L-DOPA-induced Fos-B/ΔFosB up-regulation in the motor cortex, nucleus accumbens and striatum. Finally, 7-NI blocked Fos-B/ΔFosB expression in nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-positive interneurons in the striatum. These results provide further evidence of the molecular mechanisms by which NOS-inhibiting compounds attenuate LID. The involvement of NO with DA and 5-HT neurochemistry may contribute to the understanding of this new, non-dopaminergic therapy for the management of LID., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa plant that produces antipsychotic effects in rodents and humans. It also reverses L-dopa-induced psychotic symptoms and improves motor function in Parkinson's patients. This latter effect raised the possibility that CBD could have beneficial effects on motor related striatal disorders. To investigate this possibility we evaluated if CBD would prevent catalepsy induced by drugs with distinct pharmacological mechanisms. The catalepsy test is largely used to investigate impairments of motor function caused by interference on striatal function. Male Swiss mice received acute pretreatment with CBD (5, 15, 30 or 60mg/kg, ip) 30min prior to the D2 receptor antagonist haloperidol (0.6mg/kg), the non-selective nitric oxide synthase (NOS) inhibitor L-nitro-N-arginine (L-NOARG, 80mg/kg) or the CB1 receptor agonist WIN55,212-2 (5mg/kg). The mice were tested 1, 2 or 4h after haloperidol, L-NOARG or WIN55,212-2 injection. These drugs significantly increased catalepsy time and this effect was attenuated dose-dependently by CBD. CBD, by itself, did not induce catalepsy. In a second set of experiments the mechanism of CBD effects was investigated. Thirty minutes before CBD (30mg/kg) the animals received the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). The anticataleptic effect of CBD was prevented by WAY100635. These findings indicate that CBD can attenuate catalepsy caused by different mechanisms (D2 blockade, NOS inhibition and CB1 agonism) via 5-HT1A receptor activation, suggesting that it could be useful in the treatment of striatal disorders., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Irreversible pulpitis has been associated with pain and an increase in the number of pulp inflammatory cells. Based on the action of nitric oxide (NO) elsewhere, NO may possibly participate in the sensory and autonomic innervation of the dental pulp, and may influence local inflammatory responses. The purpose of this study was to analyze normal and inflamed human dental pulp for the presence of NADPH-diaphorase (NADPH-d), as an index of NO system activity. Six non-carious second premolar pulp tissue samples were obtained from young patients who required extractions for orthodontic reasons and six inflamed samples were obtained from symptomatic carious second premolars clinically diagnosed with irreversible pulpitis. Pulp tissue was carefully removed, fixed by immersion in a cold 4% PFA buffered solution for 120 min, rinsed in cold phosphate buffer, and quickly-frozen for cryostat sectioning. Pulp tissue was sectioned perpendicularly to the vertical axis of the tooth at 20 microm and processed for histochemistry. Sections of each specimen were stained with hematoxylin-eosin and other sections were subjected to histochemical NADPH-d detection. Results indicated the presence of NADPH reactivity within the pulps of both normal and carious teeth. In the normal teeth NADPH-d activity was detected in a small number of vascular endothelial cells and fibroblasts. The inflammatory response of the pulp from carious premolars was detected in connective tissue by the presence of an increased number of fibroblasts, angioblasts and collagen fibers. It was possible to determine the extent of odontoblast reactivity since the odontoblast layer was usually absent in these split-peel preparations. There were no obvious signs of stained pulpal nerve fibers. Overall NADPH-d staining was significantly more intense within inflamed pulp tissues compared to normal healthy samples (Mann-Whitney test, p<0.002). These results suggest that NADPH-d may be used as a marker of inflammatory activity in pulpitis and provide the basis for further studies aiming to clarify the possible functions of NO in human dental pulp in pathophysiological situations.

The aim of the present study was to investigate the histological, biochemical and ultrastructural effects of occlusal alteration induced by unilateral exodontia on medial pterygoid muscle in guinea pigs, Cavia porcellus. Thirty (n=30) male guinea pigs (450g) were divided into two groups: experimental-animals submitted to exodontia of the left upper molars, and sham-operated were used as control. The duration of the experimental period was 60 days. Medial pterygoid muscles from ipsilateral and contralateral side were analyzed by histological (n=10), histochemical (n=10), and ultrastructural (n=10) methods. The data were submitted to statistical analysis. When the ipsilateral side was compared to the control group, it showed a significantly shorter neuromuscular spindle length (P<0.05), lower oxidative metabolic activity, and microvessel constriction, in spite of the capillary volume and surface density were not significantly different (P>0.05). In the contralateral side, the neuromuscular spindles showed significantly shorter length (P<0.05), the fibers reflected a higher oxidative capacity, the blood capillaries showed endothelial cell emitting slender sprouting along the pre-existing capillary, and significantly higher blood capillary surface density, and volume density (V(v)=89% Mann-Whitney test, P<0.05). This finding indicated a complex morphological and functional medial pterygoid muscle adaptation to occlusal alteration in this experimental model. Considering that neuromuscular spindles are responsible for the control of mandibular positioning and movements, the professional should consider if these changes interfere in the success of clinical procedures in medical field involving stomatognathic structures.

This study evaluated the quantity and quality of newly formed bone, stimulated by rhBMP-2 in combination with monoolein or chitosan gel as carriers, in critical bone defects created in 36 Wistar rat mandibles. Two weeks after surgery, the animals were anesthetized with 37.5% urethane submitted to perfusion and the hemi-mandibles removed for histological and histomorphometrical analysis. The results showed that there was a statistical difference between groups of animals receiving or not rhBMP-2 (p<0.05). Newly formed bone was more intense in the occlusal region, followed by the basal and middle regions, respectively. Both carriers, monoolein and chitosan gels were adequate for defect filling and control of protein release.