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Ischemia induces physiological alterations in neurons that lead to cell death. This study investigated the effects of pre-ischemic exercise on CA3 neurons. Rats were divided into three groups. Animals in the exercise group were trained 5 days a week for 4 weeks. Ischemia was induced by occlusion of both common carotid arteries (CCAs) for 20 min. Apoptotic cell death was detected by TUNEL assay. Furthermore, expression of different proteins was determined by immunohistochemical staining. The number of TUNEL-positive cells was significantly increased in the ischemia group, but pre-ischemic exercise significantly reduced apoptotic cell death (P < 0.001). In addition, our results showed a significant increase in the Bax/Bcl-2 ratio in the ischemia group. Pre-ischemic exercise attenuated this ratio (P < 0.05). Furthermore, the number of active caspase-3-positive neurons was significantly increased in the ischemia group, which was reduced markedly by exercise preconditioning (P < 0.05). This study showed that pre-ischemic exercise can exert neuroprotective effects against ischemia in CA3 neurons.

The effect of moderate hypobaric hypoxia on the expression of a peptide antioxidant Cu,Zn-superoxide dismutase in rat hippocampal neurons was evaluated in an immunocytochemical study. The expression of Cu,Zn-superoxide dismutase decreased significantly in the dorsal hippocampus (CA1 and CA2) and tended to decrease in ventral regions (CA3 and dentate gyrus) by the 24th hour after 3-fold exposure to hypoxia.

Aim: The effect of memantine administration on hippocampal neurons of the infantile rats with kaolin induced hydrocephalus was investigated., Material and Methods: Hydrocephalus was induced by injecting kaolin into the cisterna magna of 3-weeks old Sprague-Dawley rat pups. One group received a single daily dose of 20mg/kg memantine i.p. following hydrocephalus induction for a period of two weeks. By the end of the two-week period, animals were radiologically evaluated by magnetic resonance imaging and then sacrificed to get their cerebrums removed. Both immunohistochemical analysis of nitric oxide synthase activity and quantification of spared neurons in CA1, CA2 and CA3 regions of hippocampus were performed., Results: In hydrocephalus-induced rats considerable neuronal loss associated with significantly increased nitric oxide synthase immunoreactivity were determined in all hippocampal regions. However, memantine treated rats showed significantly higher number of spared neuron counts and reduced nitric oxide synthase immunoreactivity in CA1 and CA2 regions compared with the non-treated rats., Conclusion: The findings of the study show that hippocampal neurons may constitute important targets for injury secondary to hydrocephalic process in experimental infantile hydrocephalus. Early anti-excitotoxic treatment with memantine seems to have a neuroprotective effect especially in the CA1 and CA2 subunits of the hippocampus.

In the adult mouse, signaling through c-Jun N-terminal kinases (JNKs) links exposure to acute stress to various physiological responses. Inflammatory cytokines, brain injury and ischemic insult, or exposure to psychological acute stressors induce activation of hippocampal JNKs. Here we report that exposure to acute stress caused activation of JNKs in the hippocampal CA1 and CA3 subfields, and impaired contextual fear conditioning. Conversely, intrahippocampal injection of JNKs inhibitors sp600125 (30 μm) or D-JNKI1 (8 μm) reduced activity of hippocampal JNKs and rescued stress-induced deficits in contextual fear. In addition, intrahippocampal administration of anisomycin (100 μg/μl), a potent JNKs activator, mimicked memory-impairing effects of stress on contextual fear. This anisomycin-induced amnesia was abolished after cotreatment with JNKs selective inhibitor sp600125 without affecting anisomycin's ability to effectively inhibit protein synthesis as measured by c-Fos immunoreactivity. We also demonstrated milder and transient activation of the JNKs pathway in the CA1 subfield of the hippocampus during contextual fear conditioning and an enhancement of contextual fear after pharmacological inhibition of JNKs under baseline conditions. Finally, using combined biochemical and transgenic approaches with mutant mice lacking different members of the JNK family (Jnk1, Jnk2, and Jnk3), we provided evidence that JNK2 and JNK3 are critically involved in stress-induced deficit of contextual fear, while JNK1 mainly regulates baseline learning in this behavioral task. Together, these results support the possibility that hippocampal JNKs serve as a critical molecular regulator in the formation of contextual fear.

Perinatal undernutrition has adverse effects on brain physiology as well as learning and memory activity. However, the mechanism is still incompletely understood. Nitric oxide (NO) synthesized by neuronal nitric oxide synthase (nNOS) has important roles in neuronal survival and synaptic plasticity as well as contributes to the learning and memory task. The aims of the present study were to investigate whether 50% perinatal food restriction (FR50) produced deleterious effects on the population of nNOS neurons in CA1 and CA3 and the dentate gyrus (DG) region of the hippocampus using ABC immunohistochemical method. The results showed FR50 reduced body weight of offspring on postnatal day (PD)1, PD7, PD10, PD14 and PD21, and this type of food restriction impaired learning and memory of adult male offspring rats (postnatal day 70) and decreased the density of nNOS-positive cells in the CA1, CA3 and DG region of the hippocampus. These findings suggest that perinatal undernutrition affects the activity of nNOS in hippocampus. Thus, these changes in the density of nNOS neurons may partly explain learning and memory disturbances commonly observed in undernourished rats and provide clues to the knowledge of malnutrition effects upon the brain., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Prostaglandin E(2) (PGE(2)) is increased in the brain after kainic acid (KA) treatment. We previously demonstrated that KA also induces PG synthase cyclooxygenase-2 (COX-2) expression rapidly in neurons of the brain and slowly in astrocytes and endothelia. Prevention of KA-induced neuronal damage by nonneuronal COX-2 inhibition suggests a novel modulatory mechanism for neuronal injury by nonneuronal PGs. It remains unclear, however, which PG synthase is responsible for this modulation following COX-2 synthesis after neuronal insult. In addition, the PG receptor subtype that is involved in neuronal loss remains controversial. Here we demonstrate that microinjection of KA induces microsomal prostaglandin E synthase-1 (mPGES-1) in venous endothelial cells but not in neurons or astrocytes. We found that mPGES-1 plays a central role in delayed production of PGE(2) and that mPGES-1-deficient mice exhibit significantly less neuronal loss induced by KA. Furthermore, KA injection caused an increase in the immunoreactivity for the EP3 receptor in the astrocytic endfeet that surround vascular endothelia. Neurons form intimate interactions with astrocytes via glutamate, and astrocytes contact vascular endothelia through endfeet. These findings suggest that endothelial cells may control neuronal excitotoxicity, most likely by regulating astrocytes via inducible PGE(2)., (2009 Wiley-Liss, Inc.)