Focal injection of Ethidium bromide as a simple model to study cognitive deficit and its improvement

Introduction: Memory and cognitive impairments are some of devastating outcomes of Multiple Sclerosis [MS] plaques in hippocampus, the gray matter part of the brain. The present study aimed to evaluate the intrahippocampal injection of Ethidium Bromide [EB] as a simple and focal model to assess cognition and gray matter demyelination

Methods: Thirty Wistar rats were divided into three groups: control group, which received saline, as solvent of EB, into the hippocampus; and two experimental groups, which received 3 microL of EB into the hippocampus, and then, were evaluated 7 and 28 days after EB injection [n=10 in each group], using a 5-day protocol of Morris Water Maze [MWM] task as well as Transmission Electron Microscopy [TEM] assay

Results: Seven days after EB injection, the behavioral study revealed a significance increase in travelled distance for platform finding in the experimental group compared to the control group. In addition, the nucleus of oligodendrocyte showed the typical clumped chromatin, probably attributed to apoptosis, and the myelin sheaths of some axons were unwrapped and disintegrated. Twenty-eight days after EB injection, the traveled distance and the time spent in target quadrant significantly decreased and increased, respectively in experimental groups compared to the control group. Also, TEM micrographs revealed a thin layer of remyelination around the axons in 28 days lesion group

Discussion: While intracerebral or intraventricular injection of EB is disseminated in different parts of the brain and can affect the other motor and sensory systems, this model is confined locally and facilitates behavioral study. Also, this project could show improvement of memory function subsequent to the physiological repair of the gray matter of the hippocampus

Upregulation of connexins 30 and 32 gap junctions in rat hippocampus at transcription level by chronic central injection of lipopolysaccharide

Gap junctions composed of connexins [Cx] are functional in cell defense by propagation of toxic/death molecules to neighboring cells. Hippocampus, one of the brain regions with particular vulnerability to damage, has a wide network of gap junctions. Functional response of astrocytic Cx30 and neuronal Cx32 to hippocampal damage is unknown. We infused lipopolysaccharide [LPS] intracerebroventricularly [2.5 microg/rat] once daily for two weeks to create neuroinflammation. The mRNA and protein levels of the Cx were measured in the hippocampus after 1[st], 7[th] and 14[th] injection by real-time PCR and Western-blot techniques. A significant increase in Cx32 and Cx30 gene expression was observed after 7[th] and 14[th] injection of LPS with no significant change in their protein abundance. Transcriptional overexpression of hippocampal Cx30 and Cx32 could be an adaptive response to production of intracellular toxic molecules but it is not accompanied with post- transcriptional overexpression and might have no functional impact

Zingiber officinale alters 3,4-methylenedioxymeth amphetamine-induced neurotoxicity in rat brain

The spice Zingiber officinale or ginger possesses antioxidant activity and neuroprotective effects. The effects of this traditional herbal medicine on 3,4-methylenedioxymethamphetamine [MDMA] induced neurotoxicity have not yet been studied. The present study considers the effects of Zingiber officinale on MDMA-induced spatial memory impairment and apoptosis in the hippocampus of male rats. In this experimental study, 21 adult male Sprague Dawley rats [200-250 g] were classified into three groups [control, MDMA, and MDMA plus ginger]. The groups were intraperitoneally administered 10 mg/kg MDMA, 10 mg/kg MDMA plus 100 mg/kg ginger extract, or 1 cc/kg normal saline as the control solution for one week [n=7 per group]. Learning memory was assessed by Morris water maze [MWM] after the last administration. Finally, the brains were removed to study the cell number in the cornu ammonis [CA1] hippocampus by light microscope, Bcl-2 by immunoblotting, and Bax expression by reverse transcription polymerase chain reaction [RT-PCR]. Data was analyzed using SPSS 16 software and a one-way ANOVA test. Escape latency and traveled distances decreased significantly in the MDMA plus ginger group relative to the MDMA group [p<0.001]. Cell number increased in the MDMA plus ginger group in comparison to the MDMA group. Down-regulation of Bcl-2 and up-regulation of Bax were observed in the MDMA plus ginger group in comparison to the MDMA group [p<0.05]. Our findings suggest that ginger consumption may lead to an improvement of MDMA-induced neurotoxicity

Effect of chronic intracerebroventricluar administration of lipopolysaccharide on connexin43 protein expressionin rat hippocampus

Hippocampal damages, which are accompanied by inflammation, are among the main causes of epilepsy acquisition. We previously reported that chronic intracerebroventricular [i.c.v.] injection of lipopolysaccharide [LPS] modulates epileptogenesis in rats. There is a network of gap junction channels in the hippocampus that contribute to epileptogenesis. Gap junction channels are formed by oligomeric protein subunits called connexins [Cx]. Astrocytic Cx43 and neuronal Cx36 are expressed in the hippocampus. In order to find out the possible role of gap junctions in seizure-modulating effect of LPS and neuroinflammation, we studied the effect of central administration of LPS on expression of Cx36 and Cx43 in rat hippocampus. LPS, 2.5 micro g/rat/day, was injected i.c.v. to male Wistar rats for 14 days. mRNA and protein abundance of Cx36, Cx43 and IL1-beta were measured in rat hippocampus by real time-PCR, Western blot and ELISA techniques, at the beginning, in the middle, and at the end of the treatment period. IL1-beta protein level was significantly increased 6 h after first injection of LPS. Cx36 and Cx43 mRNA expression did not alter during chronic administration of LPS. A selective decrease in Cx43 protein expression was observed after 7 injections of LPS. It is suggested that Cx43 containing gap junctions in the hippocampus is down-regulated in response to chronic injection of LPS. This event can inhibit propagation of toxic and noxious molecules to neighboring cells and modulate hippocampal excitability and epileptogenesis