Gerbil Brain Research Articles

Study on the Difference of Protective Efficacy and Mechanism of Radix Aconiti Coreani and Rhizoma Typhonii in Gerbils with Ischemic Stroke.

Ischemic stroke is a common type of stroke, but effective treatment methods are still imperfect and new effective therapies need to be explored. Radix Aconiti Coreani and Rhizoma Typhonii used as Baifuzi in the treatment of stroke or symptoms associated with stroke have been recorded in ancient Chinese books and are widely used. Modern pharmacological studies have demonstrated that both of them have antioxidant and anti-inflammatory effects. The purpose of this study is to investigate whether Radix Aconiti Coreani and Rhizoma Typhonii have therapeutical effects on gerbils with ischemic stroke, to investigate their potential mechanisms of action, and to provide a reference for rational clinical application by comparing the differences between them. In this manuscript, the right unilateral ligation of the carotid artery of gerbils was used to cause an ischemic stroke model. The neurological deficits of gerbils in each group were scored by Longa scale. The area of cerebral infarction was detected by 2,3,5-tribenzotetrazolchloride staining. The levels of inflammatory factors, oxidative stress indexes, and vascular endothelial function indexes in brain homogenate and serum were determined by ELISA. The expression levels of P-Akt PI3K, HO-1, and KEAP1 proteins in brain tissue were determined by Western blot. Immunofluorescence staining was used to observe the recovery of neuronal cells in the hippocampal CA1 region of the gerbil brain tissue and the expression of proteins related to PI3K/Akt and KEAP1/Nrf2 signaling pathways in neuronal cells in the hippocampal CA1 region. It was found that Radix Aconiti Coreani and Rhizoma Typhonii could improve neurological deficits and reduce cerebral infarction rate in gerbils. The results showed that Radix Aconiti Coreani and Rhizoma Typhonii could significantly decrease the expression of inflammatory factors, increase the expression of antioxidative stress indexes and vascular endothelial function factors, activate the PI3K/Akt, KEAP1/Nrf2 signaling pathway, reduce the inflammatory response, inhibit the oxidative stress, enhance the vascular endothelial cell function, and thus protect against ischemic brain injury. From the experimental results, both Radix Aconiti Coreani and Rhizoma Typhonii had neuroprotective effects on ischemic brain injury. Compared with Rhizoma Typhonii, the effects of Radix Aconiti Coreani on anti-inflammatory and antioxidative stress were more significant, while Rhizoma Typhonii had showed more significant effects in promoting angiogenesis after ischemic stroke by increasing the level of NO.

Chronic social defeat alters behaviors and neuronal activation in the brain of female Mongolian gerbils

Chronic social defeat has been found to be stressful and to affect many aspects of the brain and behaviors in males. However, relatively little is known about its effects on females. In the present study, we examined the effects of repeated social defeat on social approach and anxiety-like behaviors as well as the neuronal activation in the brain of sexually naïve female Mongolian gerbils (Meriones unguiculatus). Our data indicate that repeated social defeats for 20 days reduced social approach and social investigation, but increased risk assessment or vigilance to an unfamiliar conspecific. Such social defeat experience also increased anxiety-like behavior and reduced locomotor activity. Using ΔFosB-immunoreactive (ΔFosB-ir) staining as a marker of neuronal activation in the brain, we found significant elevations by social defeat experience in the density of ΔFosB-ir stained neurons in several brain regions, including the prelimbic (PL) and infralimbic (IL) subnuclei of the prefrontal cortex (PFC), CA1 subfields (CA1) of the hippocampus, central subnuclei of the amygdala (CeA), the paraventricular nucleus (PVN), dorsomedial nucleus (DMH), and ventrolateral subdivision of the ventromedial nucleus (VMHvl) of the hypothalamus. As these brain regions have been implicated in social behaviors and stress responses, our data suggest that the specific patterns of neuronal activation in the brain may relate to the altered social and anxiety-like behaviors following chronic social defeat in female Mongolian gerbils.

Validation of the Reference Genes for Expression Analysis in the Hippocampus after Transient Ischemia/Reperfusion Injury in Gerbil Brain.

Transient brain ischemia in gerbils is a common model to study the mechanisms of neuronal changes in the hippocampus. In cornu ammonnis 2-3, dentate gyrus (CA2-3,DG) regions of the hippocampus, neurons are resistant to 5-min ischemia/reperfusion (I/R) insult, while cornu ammonnis 1 (CA1) is found to be I/R-vulnerable. The quantitative polymerase chain reaction (qRT-PCR) is widely used to study the expression of genes involved in these phenomena. It requires stable and reliable genes for normalization, which is crucial for comparable and reproducible analyses of expression changes of the genes of interest. The aim of this study was to determine the best housekeeping gene for the I/R gerbil model in two parts of the hippocampus in controls and at 3, 48, and 72 h after recanalization. We selected and tested six reference genes frequently used in central nervous system studies: Gapdh, Actb, 18S rRNA, Hprt1, Hmbs, Ywhaz, and additionally Bud23, using RefFinder, a comprehensive tool based on four commonly used algorithms: delta cycle threshold (Ct), BestKeeper, NormFinder, and geNorm, while Hprt1 and Hmbs were the most stable ones in CA2-3,DG. Hmbs was the most stable in the whole hippocampal formation. This indicates that the general use of Hmbs, especially in combination with Gapdh, a highly expressed reference gene, seems to be suitable for qRT-PCR normalization in all hippocampal regions in this model.

Phosphoglycerate kinase 1 protects against ischemic damage in the gerbil hippocampus.

Phosphoglycerate kinase 1 (PGK1) is a metabolic enzyme that converts 1,3-diphosphoglycerate to 3-phosphoglycerate. In the current study, we synthesized a PEP-1-PGK1 fusion protein that can cross the blood-brain barrier and cell membrane, and the effects of PEP-1-PGK1 against oxidative stress were investigated HT22 cells and ischemic gerbil brain. The PEP-1-PGK1 protein and its control protein (Con-PGK1) were treated and permeability was evaluated HT22 cells. The PEP-1-PGK1 was introduced into HT22 cells depending on its concentration and incubation time and was gradually degraded over 36 h after treatment. PEP-1-PGK1, but not Con-PGK1, significantly ameliorated H2O2-induced cell damage and reactive oxygen species formation in HT22 cells. Additionally, PEP-1-PGK1, but not Con-PGK1, mitigated ischemia-induced hyperlocomotion 1 d after ischemia and 4 d after ischemia of neuronic cell death. PEP-1-PGK1 treatment significantly alleviated the raised lactate and succinate dehydrogenase activities in the early (15 min to 6 h) and late (4 and 7 d) stages of ischemia, respectively. In addition, PEP-1-PGK1 treatment ameliorated the decrease in ATP and pH levels in the late stage (2-7 d) of ischemia. Nuclear factor erythroid-2-related factor 2 (Nrf2) levels accelerated the ischemia-induced increase in the hippocampus 1 d after ischemia after PEP-1-PGK1 treatment. Neuroprotective and ameliorative effects were prominent at a low concentration (0.1 mg/kg), but not at a high concentration (1 mg/kg), of PEP-1-PGK1. Collectively, low concentrations of PEP-1-PGK1 prevented neuronal stress by increasing energy production.

Therapeutic Effects of Risperidone against Spinal Cord Injury in a Rat Model of Asphyxial Cardiac Arrest: A Focus on Body Temperature, Paraplegia, Motor Neuron Damage, and Neuroinflammation.

Cardiac arrest (CA) causes severe spinal cord injury and evokes spinal cord disorders including paraplegia. It has been reported that risperidone, an antipsychotic drug, effectively protects neuronal cell death from transient ischemia injury in gerbil brains. However, until now, studies on the effects of risperidone on spinal cord injury after asphyxial CA (ACA) and cardiopulmonary resuscitation (CPR) are not sufficient. Therefore, this study investigated the effect of risperidone on hind limb motor deficits and neuronal damage/death in the lumbar part of the spinal cord following ACA in rats. Mortality, severe motor deficits in the hind limbs, and the damage/death (loss) of motor neurons located in the anterior horn were observed two days after ACA/CPR. These symptoms were significantly alleviated by risperidone (an atypical antipsychotic) treatment after ACA. In vehicle-treated rats, the immunoreactivities of tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1β), as pro-inflammatory cytokines, were increased, and the immunoreactivities of IL-4 and IL-13, as anti-inflammatory cytokines, were reduced with time after ACA/CPR. In contrast, in risperidone-treated rats, the immunoreactivity of the pro-inflammatory cytokines was significantly decreased, and the anti-inflammatory cytokines were enhanced compared to vehicle-treated rats. In brief, risperidone treatment after ACA/CPR in rats significantly improved the survival rate and attenuated paralysis, the damage/death (loss) of motor neurons, and inflammation in the lumbar anterior horn. Thus, risperidone might be a therapeutic agent for paraplegia by attenuation of the damage/death (loss) of spinal motor neurons and neuroinflammation after ACA/CPR.

Astrocyte specific proteins content in the different parts of the rat and mongolian gerbil brain during ontogenesis

Astrocyte specific proteins content in the different parts of the rat and mongolian gerbil brain during ontogenesis

Shear Stress Rescued the Neuronal Impairment Induced by Global Cerebral Ischemia Reperfusion via Activating PECAM-1-eNOS-NO Pathway.

Microvessel hypoperfusion following ischemic stress resulted in a decreased shear stress of brain microvascular endothelial cells (BMECs) and contributed to abnormal expression of PECAM-1 after global cerebral ischemia/reperfusion (I/R) injury. Here, we identified novel pathophysiologic and rehabilitative procedures specific to shear stress in microvascular endothelial cells in response to global cerebral I/R injury. We found that the decrease in cerebral blood flow of gerbils after global cerebral I/R injury reduces shear stress, and the abnormal change in shear stress leads to microvascular endothelial cell and neuron damage. Nevertheless, suitable high levels of shear stress contribute to rescuing the dysfunction and malformation of BMECs via regulating the PECAM-1-eNOS-NO pathway to enhance nitric oxide release, decrease the expression of caspase-3 to reduce apoptosis, and improve the shear-adaptability of endothelial cells, thereby playing a protective role in the gerbil brain.

Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11/GPX4 axis in gerbils

AimsTo evaluate the impact of galangin treatment on cerebral ischemia-reperfusion (I/R) injury in gerbils and to identify potential mechanisms of the protective effect of galangin on hippocampal neurons after I/R injury. Principal methodsA cerebral ischemia model using bilateral common carotid artery ligation in gerbils was established. The Morris water maze (MWM) test was used to evaluate the learning and memory ability of gerbils. The cell viability was evaluated with an MTT assay. The levels of lipid peroxide biomarkers were measured to estimate the injury due to lipid peroxide. The morphology was detected by electron micrography, immunofluorescence and Nissl staining. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to measure the molecular characteristics. Key findingsIn the MWM, gerbils treated with galangin after I/R injury showed significant improvements in learning and memory. In addition, galangin treatment reduced the levels of lipid peroxide in the brains of gerbils that underwent I/R as well as reduced the amount of cell death and increased the expression of SLC7A11 and glutathione peroxidase 4 (GPX4). Furthermore, the expression of the marker of ferroptosis was decreased in galangin-treated gerbils, and the effect of galangin was weakened when SLC7A11 was knocked down. These results show that galangin can inhibit ferroptosis by enhancing the expressions of SLC7A11 and GPX4 as well as reduce neuronal cell death. SignificanceGalangin inhibits ferroptosis through activation of the SLC7A11/GPX4 axis and has a protective effect on hippocampal neurons in gerbils after I/R.

Differences in the number of oxytocin, vasopressin, and tyrosine hydroxylase cells in brain regions associated with mating among great, midday, and Mongolian gerbils

Neurotransmitters, such as oxytocin (OT), vasopressin (AVP), and dopamine (DA), within the mesolimbic system have deeply conserved roles in regulating mating-related behaviors. However, comparative studies among monogamous and polygamous animals focus mainly on Microtus; very little research has been done in gerbils. Here, we measured body weight, body length, tail length, serum hormone concentrations, and the immunoreactive (ir)-cells of OT, AVP, and tyrosine hydroxylase (TH) in the brain of the polygamous great gerbil (Rhombomys opimus), midday gerbil (Meriones meridianus), and monogamous Mongolian gerbil (Meriones unguiculatus). Body weight, body length, tail length, and serum AVP concentrations were greater in the great gerbil than in the midday gerbil and Mongolian gerbil. The number of OT and AVP cells in the para ventricular nucleus (PVN) and supra optic nucleus (SON) of the hypothalamus were greater in the Mongolian gerbil than in the great gerbil and midday gerbil. Similarly, the number of TH cells in the PVN, medial preoptic area (MPOA), and ventral tegmental area (VTA) was greater in the Mongolian gerbil than in the great gerbil and midday gerbil. To summarize, the number of OT and AVP cells in the PVN and SON and TH cells in the PVN, MPOA, and VTA in the monogamous Mongolian gerbil are greater than those in the great gerbil and midday gerbil.

Experimental infection by Neospora caninum in gerbil reduces activity of enzymes involved in energy metabolism

Neospora caninum is a protozoan that has tropism for the central nervous system. The aim of this study was to determine whether experimental infection of gerbils would interfere with activity of enzymes associated with energy metabolism. We randomized 20 gerbils into two groups (ten animals per group): the control group (healthy animals; uninfected) and the infected group (experimentally infected with dose 7.8 × 102 tachyzoites of N. caninum per gerbil). On day six and twelve post-infection (PI), brain and spleen tissues were collected for biochemical and histopathological analyses. No histopathological lesions were observed in the brains of infected animals; however, inflammatory infiltrates were found in the spleen. Significantly greater levels of reactive oxygen species (ROS) were observed in the brain and spleen of infected gerbils than in the control group at 12 days PI. Cytosolic creatine kinase (CK-CYT), mitochondrial creatine kinase (CK-MIT), and pyruvate kinase (PK) activities were lower in the brains of infected gerbils than in those of the control group on day 12 PI. There was significantly less CK-CYT activity in the spleens of infected gerbils on day 6 and 12 PI. Finally, there was significantly less sodium-potassium ion pump (Na+/K+ ATPase) activity in the brains and spleens of infected gerbils on day 12 PI. These data suggest that experimental infection with N. caninum interfered with energy metabolism associated with ATP homeostasis in the brain and spleen, directly or indirectly, apparently mediated by ROS overproduction, contributing to inhibition of Na+/K+ ATPase activity.

Risperidone Treatment after Transient Ischemia Induces Hypothermia and Provides Neuroprotection in the Gerbil Hippocampus by Decreasing Oxidative Stress.

Compelling evidence from preclinical and clinical studies has shown that mild hypothermia is neuroprotective against ischemic stroke. We investigated the neuroprotective effect of post-risperidone (RIS) treatment against transient ischemic injury and its mechanisms in the gerbil brain. Transient ischemia (TI) was induced in the telencephalon by bilateral common carotid artery occlusion (BCCAO) for 5 min under normothermic condition (37 ± 0.2 °C). Treatment of RIS induced hypothermia until 12 h after TI in the TI-induced animals under uncontrolled body temperature (UBT) compared to that under controlled body temperature (CBT) (about 37 °C). Neuroprotective effect was statistically significant when we used 5 and 10 mg/kg doses (p < 0.05, respectively). In the RIS-treated TI group, many CA1 pyramidal neurons of the hippocampus survived under UBT compared to those under CBT. In this group under UBT, post-treatment with RIS to TI-induced animals markedly attenuated the activation of glial cells, an increase of oxidative stress markers [dihydroethidium, 8-hydroxy-2′ -deoxyguanosine (8-OHdG), and 4-Hydroxynonenal (4-HNE)], and a decrease of superoxide dismutase 2 (SOD2) in their CA1 pyramidal neurons. Furthermore, RIS-induced hypothermia was significantly interrupted by NBOH-2C-CN hydrochloride (a selective 5-HT2A receptor agonist), but not bromocriptine mesylate (a D2 receptor agonist). Our findings indicate that RIS-induced hypothermia can effectively protect neuronal cell death from TI injury through attenuation of glial activation and maintenance of antioxidants, showing that 5-HT2A receptor is involved in RIS-induced hypothermia. Therefore, RIS could be introduced to reduce body temperature rapidly and might be applied to patients for hypothermic therapy following ischemic stroke.

The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation

ObjectiveCerebral ischemia is the most common type of neuronal injury and is characterized by a reduction in the function and number of hippocampal neurons. Carvacrol has a significant neuroprotective effect in cerebral ischemia. However, the mechanisms by which carvacrol affects cerebral ischemia, especially with respect to the regulation of neuronal damage by iron levels, have never been systematically studied. This study aimed to reveal the mechanisms by which carvacrol protects against hippocampal neuron impairment after ischemic stroke in gerbils. Materials and methodsThe Morris water maze test was performed to evaluate learning and memory impairments. Iron ion content and oxidative stress index were detected by the kit. MTT assay was performed to assess the cell viability. The morphology and molecular characteristics were detected by electron micrographs and western blot. ResultsIn the present study, we demonstrated the neuroprotective effects of carvacrol in vivo and in vitro. The Morris water maze test showed that the learning and memory abilities of the gerbils treated with carvacrol were significantly improved. Lipid peroxide injury was evaluated by measuring the levels of lipid peroxide biomarkers; the results indicated that carvacrol decreased the level of lipid peroxide in ischemic gerbil brain tissue. Histopathological examinations and western blotting were performed to evaluate injury in neurons, and carvacrol reduced cell death. Moreover, ferroptosis in the hippocampus was evaluated by measuring the levels of proteins involved in this iron-dependent form of regulated cell death. These results indicated that carvacrol reduced cell death and that carvacrol inhibited ferroptosis by increasing the expression of glutathione peroxidase 4(GPx4). This study showed that carvacrol may be a valuable drug for treating cerebral ischemia. ConclusionCarvacrol provides protection for hippocampal neurons against I/R in gerbils by inhibiting ferroptosis through increasing the expression of GPx4.

Risperidone treatment after transient ischemia induces hypothermia via 5-HT2aAntagonism and provides neuroprotection in the gerbil hippocampus by decreasing oxidative stress

Background: Compelling evidence from preclinical and clinical studies has shown that mild hypothermia is neuroprotective against ischemic stroke. We investigated neuroprotectiveeffect of post-risperidone (RIS) treatment against transient ischemic injury and its mechanisms in the gerbil brain.

Decrease in glucose transporter 1 levels and translocation of glucose transporter 3 in the dentate gyrus of C57BL/6 mice and gerbils with aging

In the present study, we compared the cell-specific expression and changes protein levels in the glucose transporters (GLUTs) 1 and 3, the major GLUTs in the mouse and gerbil brains using immuno-histochemistry and Western blot analysis. In both mouse and gerbils, GLUT1 immunoreactivity was mainly found in the blood vessels in the dentate gyrus, while GLUT3 immunoreactivity was detected in the subgranular zone and the molecular layer of the dentate gyrus. GLUT1-immunoreactivity in blood vessels and GLUT1 protein levels were significantly decreased with age in the mice and gerbils, respectively. In addition, few GLUT3-immunoreactive cells were found in the subgranular zone in aged mice and gerbils, but GLUT3-immunoreactivity was abundantly found in the polymorphic layer of dentate gyrus in mice and gerbils with a dot-like pattern. Based on the double immunofluorescence study, GLUT3-immunoreactive structures in gerbils were localized in the glial fibrillary acidic protein-immunoreactive astrocytes in the dentate gyrus. Western blot analysis showed that GLUT3 expression in the hippocampal homogenates was slightly, although not significantly, decreased with age in mice and gerbils, respectively. These results indicate that the reduction in GLUT1 in the blood vessels of dentate gyrus and GLUT3 in the subgranular zone of dentate gyrus may be associated with the decrease in uptake of glucose into brain and neuroblasts in the dentate gyrus. In addition, the expression of GLUT3 in the astrocytes in polymorphic layer of dentate gyrus may be associated with metabolic changes in glucose in aged hippocampus.

ITRAQ-based differential proteomic analysis in Mongolian gerbil brains chronically infected with Toxoplasma gondii

The aim of our study was to detect differentially regulated proteins and specific signaling pathways in Mongolian gerbil brains during chronic Toxoplasma gondii (T.gondii) PRU strain infection. We use a iTRAQ-based strategy to detecte 4935 proteins, out of which 110 proteins were differentially expressed (>/=2.0-fold, p value <0.05) when the brain of gerbils infected with T.gondii was compared to control brain tissues. We confirmed the authenticity and the accuracy of iTRAQ results through quantitative real-time PCR and western blot (WB), which was consistent with mass spectrometry analysis. Pathway analysis and GO (Gene Ontology) annotations indicated the deregulation of several pathways related to immune response, metabolism and neurological processes, like neuronal growth and neurotransmitter transport. Through the iTRAQ-based strategy, we obtained a comparative proteome profile of brain tissues from Mongolian gerbils with chronic infection of T.gondii. Several differentially expressed proteins involved in neurological pathways, like Parvalbumin, Drebrin or Synaptotagmin, can be further investigated to enhance our understanding of central nervous system (CNS) injury caused by T.gondii. Biological significanceT.gondii can infect almost all nucleated cells with a preference for the CNS, which can induce Toxoplasma encephalitis (TE). However, the pathogenesis and mechanisms between the parasite and host associated with TE are largely unexplored. Around 30% of the world population is considered to have latent infection with T.gondii and >90% patients died of TE, while the proportion of secondary paralysis is also high. Patients of TE may have highly varied neurological symptoms with both focal and diffuse neurological lesions, while mental symptoms and behavior disorders are frequently accompanied, like the Alzheimer's disease (AD). We present a comparative proteomics analysis to explore the differences of protein expression caused by chronic T.gondii infection. The results of this analysis can be helpful for identifying key proteins involved in the pathogenesis of TE. In addition, the study can contribute to a better understanding of molecular mechanisms underlying the host–parasite relationship in chronic infection of T.gondii and facilitate further development of new therapies for TE.

The organization of frequency and binaural cues in the gerbil inferior colliculus.

The inferior colliculus (IC) is the common target of separate pathways that transmit different types of auditory information. Beyond tonotopy, little is known about the organization of response properties within the 3-dimensional layout of the auditory midbrain in most species. Through study of interaural time difference (ITD) processing, the functional properties of neurons can be readily characterized and related to specific pathways. To characterize the representation of ITDs relative to the frequency and hodological organization of the IC, the properties of neurons were recorded and the sites recovered histologically. Subdivisions of the IC were identified based on cytochrome oxidase (CO) histochemistry. The results were plotted within a framework formed by an MRI atlas of the gerbil brain. The central nucleus was composed of two parts, and lateral and dorsal cortical areas were identified. The lateral part of the central nucleus had the highest CO activity in the IC and a high proportion of neurons sensitive to ITDs. The medial portion had lower CO activity and fewer ITD-sensitive neurons. A common tonotopy with a dorsolateral to ventromedial gradient of low to high frequencies spanned the two regions. The distribution of physiological responses was in close agreement with known patterns of ascending inputs. An understanding of the 3-dimensional organization of the IC is needed to specify how the single tonotopic representation in the IC central nucleus leads to the multiple tonotopic representations in core areas of the auditory cortex.

Hyperbaric oxygen and hyperbaric air preconditioning induces ischemic tolerance to transient forebrain ischemia in the gerbil

Ischemic preconditioning with sublethal stress triggers defensive mechanisms against ischemic brain damage; however, such manipulations are potentially dangerous and, therefore, safe stimuli have been sought. Hyperoxia preconditioning by administration of hyperbaric (HBO) or normobaric oxygen (NBO) may have neuroprotective potential. The aim of this study was to determine whether preconditioning with HBO and air (HBA) applied at 2.5 absolute pressure (ATA) or NBO preconditioning induces ischemic tolerance in the brain of gerbils subjected to 3min transient cerebral ischemia. Neuronal cell survival, changes in brain temperature, the generation of factors involved in neurodegeneration and basic behavior in nest building were all tested. Hyperoxic preconditioning prevented ischemia-induced neuronal cell loss, reduced the number of TUNEL positive cells in the CA1 region of the hippocampus and improved the nest building process compared to untreated ischemic animals. Preconditioning also suppressed the production of reactive oxygen species and increased Bax expression normally observed after an ischemic episode. Only HBO preconditioning inhibited ischemia-evoked increases in brain temperature. Our results show that hyperoxic preconditioning results in induction of ischemic tolerance and prevents ischemia-induced neuronal damage in the gerbil brain. Pressurized air preconditioning was as effective as HBO or NBO preconditioning in providing neuroprotection. The observed neuroprotection probably results from mild oxidative stress evoked by increased brain tissue oxidation and activation of antioxidant and antiapoptotic defenses.

Evidence of Hepatitis E virus breaking through the blood-brain barrier and replicating in the central nervous system.

Neurologic dysfunctions such as Guillain-Barre' syndrome, encephalitis, meningitis and transverse myelitis occur frequently in patients with hepatitis E virus (HEV) infection, and this study was conducted to better characterize the role of HEV in the pathogenesis of neurologic disorders. Genotype 4 strain of swine HEV was used to inoculate Mongolian gerbils. Reverse transcription-nested polymerase chain reaction (RT-nPCR), ELISA, histopathology, ultrastructural pathology and enzyme immunohistochemistry method were conducted to investigate the replication and localization of HEV in the central nervous system (CNS) and the consequent pathological changes. Both positive- and negative-strand HEV RNA was detectable in brain and spinal cord from 7 to 28 dpi (days postinoculation) via RT-nPCR. Various pathological changes such as perineural invasion, neuron necrosis, microglia nodule, lymphocyte infiltration, perivascular cuff and myelin degeneration were observed in HEV-positive brains and spinal cords. Immunohistochemical (IHC) staining targeting on HEV ORF2 protein revealed positive signals concentrated mainly in the cytoplasm of neuron, ependymal epithelium and choroid plexus area. Positive area density of ZO-1 (zonula occludens-1) in brain of HEV-positive gerbils decreased, while the GFAP (glial fibrillary acidic protein) expression was upregulated compared with control groups. These results provide strong evidence that HEV is able to damage the blood-brain barrier (BBB), replicate in brain and spinal cord, and hammer the causative role of HEV in the pathogenesis of neurologic disorders.

THE CHANGES OF GLIAL FIBRILLARY ACID PROTEIN LEVEL IN THE DIFFERENT BRAIN AREAS OF GERBILS UNDER DEVELOPMENT, AGING AND ALPHA-KETO GLUTARATE EFFECT

There has been shown the change of level of astrocytes-specific glial fibrillary acid protein (GFAP) in different areas of the brain of laboratory gerbils at different stages of postnatal development, aging, and the effect of lphaketoglutarate.Studies have shown that the content of both soluble and filament forms of GFAP significantly increased during the first 30 days of postnatal development in all parts of the brain. After 30 days, the level of soluble forms of GFAP continued gradualy increase in all studied brain areas of gerbils during development and aging. Content of filament forms of GFAP in the gerbils brain after 90 days has a different tendency to change depending on the brain region. The long-term diet containing 2% alpha-ketoglutarate has been prevented overproduction of filament form of GFAP in the thalamus and hippocampus of older animals.

Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628.

Background:Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein.Methods:A novel neurokinin 3 receptor radioligand, [18F]Lu AF10628 ((S)-N-(cyclobutyl(3-fluorophenyl)methyl)-8-fluoro-2-((3-[18F]-fluoropropyl)amino)-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey.Results:The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding.Conclusion:Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties.