Expression Of Glial Fibrillary Acidic Protein In Hippocampus Research Articles

Protection by Neostigmine and Atropine Against Brain and Liver Injury Induced by Acute Malathion Exposure.

We examined the effect of treatment with neostigmine alone or with atropine on brain oxidative stress and on brain and liver tissue damage following acute malathion toxicity. Rats were intraperitoneally treated with malathion 150 mg/kg along with neostigmine (200 or 400 μg/kg) or neostigmine (200 μg/kg) + atropine (1 mg/kg) and euthanized 4 h later. Results indicated that compared with the saline group, malathion resulted in (i) higher brain malondialdehyde (MDA) and nitric oxide (46.4% and 86.2%); (ii) decreased brain reduced glutathione (GSH) (67.6%); (iii) decreased brain paraoxonase-1 (PON1), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (31.2%, 21.6% and 60%); (iv) decreased brain glucose (-38.1%); (v) neuronal degeneration in cortex and hippocampus and markedly increased glial fibrillary acidic protein (GFAP) immunostaining in the hippocampus; (v) hydropic and fatty degeneration in liver. Rats treated with malathion along with neostigmine or neostigmine + atropine showed no change in brain MDA but decreased nitric oxide (-34.2%-48%). GSH increased after neostigmine 200 μg/kg or neostigmine + atropine (35.8% and 41%). PON1 activity increased (42%-35.2%) and glucose concentrations increased (91.5%-81.5%) by 400 μg/kg neostigmine or neostigmine + atropine. Brain AChE activity remained unchanged but BChE activity showed 18.3% increment after 400 μg/kg neostigmine. Rats treated with 400 μg/kg neostigmine or neostigmine + atropine had normal neuronal appearance in cortex and hippocampus and weak GFAP expression in hippocampus. Liver damage was prevented by neostigmine + atropine. These results suggest that treatment with neostigmine + atropine afforded protection against the deleterious effects of acute malathion on the brain and liver.

Effects of kaixin jieyu decoction on behavior and glial fibrillary acidic protein expression in cerebral hippocampus of a rat vascular depression model.

To explore the effects and anti-depression mechanisms of Kaixin Jieyu Decoction (, KJD). The rat vascular depression (VD) model was established by ligation of bilateral common carotid arteries (LBCCA) combined with chronic unpredictable mild stress (CUMS). Forty Wistar rats were randomly divided into sham, VD model, VD + high-dose KJD [15.4 g/(kg·d) of crude drug], VD + medium-dose KJD [7.7 g/(kg·d) of crude drug], and VD + fluoxetine [2.4 mg/(kg·d)] groups (n=8 in each group), and the treatments lasted for 21 days. Changes of behavior and hippocampus pathology were observed. The level of glial fibrillary acidic protein (GFAP) protein and mRNA in hippocampus was detected respectively by immunohistochemistry and real-time polymerase chain reaction. Compared with the sham group, rats in model group showed a variety of behavioral obstacles, including a significant reduction in sucrose consumption percentage, horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01), pathological damage like neuronal degeneration, necrosis, and a significant decrease of GFAP protein and mRNA in hippocampus (P<0.01); compared with the model group, rats in the high-dose KJD group, medium-dose KJD group and fluoxetine group obtained notable higher behavioral scores, and pathological injury lessened in hippocampus with a increased expression of GFAP protein and mRNA P<0.05 or P<0.01); compared with the medium-dose KJD group and fluoxetine group, GFAP mRNA in high-dose KJD group expressed higer (P<0.05). LBCCA combined with CUMS may cause depression-like behavioral changes resulting in the VD model of rats whose depression state can be ameliorated by KJD, and the mechanism of cerebral protection is related possibly with promoting expression of GFAP in hippocampus.

Cerebrospinal Fluid Protein Biomarker Panel for Assessment of Neurotoxicity Induced by Kainic Acid in Rats

Glutamate excitotoxicity plays a key role in the etiology of a variety of neurological, psychiatric, and neurodegenerative disorders. The goal of this study was to investigate spatiotemporal distribution in the brain and cerebrospinal fluid (CSF) concentrations of ubiquitin C-terminal hydrolase-1 (UCH-L1), glial fibrillary acidic protein (GFAP), αII-spectrin breakdown products (SBDP150, SBDP145, and SBDP120), and their relationship to neuropathology in an animal model of kainic acid (KA) excitotoxicity. Triple fluorescent labeling and Fluoro-Jade C staining revealed a reactive gliosis in brain and specific localization of degenerating neurons in hippocampus and entorhinal cortex of KA-treated rats. Immunohistochemistry showed upregulation of GFAP expression in hippocampus and cortex beginning 24h post KA injection and peaking at 48h. At these time points concurrent with extensive neurodegeneration all SBDPs were observed throughout the brain. At 24h post KA injection, a loss of structural integrity was observed in cellular distribution of UCH-L1 that correlated with an increase in immunopositive material in the extracellular matrix. CSF levels of UCH-L1, GFAP, and SBDPs were significantly increased in KA-treated animals compared with controls. The temporal increase in CSF biomarkers correlated with brain tissue distribution and neurodegeneration. This study provided evidence supporting the use of CSF levels of glial and neuronal protein biomarkers to assess neurotoxic damage in preclinical animal models that could prove potentially translational to the clinic. The molecular nature of these biomarkers can provide critical information on the underlying mechanisms of neurotoxicity that might facilitate the development of novel drugs and allow physicians to monitor drug safety.

Alterations of glial fibrillary acidic protein expression and neural apoptosis in brain of rat offspring born by cesarean section

To study changes of glial fibrillary acidic protein (GFAP) expression and neural apoptosis in rat hippocampus and cortex of cesarean delivered offspring. Thirty-eight pregnant SD rats were randomly allocated into 2 groups: 19 rats in vaginal delivery (VD) and 19 rats in cesarean section (CS). Forty-eight fetuses born by VD were kept intact, 40 fetuses were delivered by CS on day 21 of gestation. The fetal brain tissues were taken out on postnatal day 30 and 115, the expression profiles of GFAP in hippocampus and cortex were measured by immunohistochemical staining and western blot. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. (1) The expression profiles of GFAP: on postnatal day 115, the mean number of GFAP-immunoreactive astrocytes of hippocampus 29.7 ± 10.9 in VD group was significantly lower than 36.2 ± 2.8 in CS group (P < 0.05). The average GFAP-positive cells in the cortex of frontal lobe of 23.2 ± 4.6 in VD group was significantly lower than 36.8 ± 5.9 in CS group (P < 0.01). Likewise, on postnatal day 30, the mean number of GFAP-immunoreactive astrocytes of frontal cortex of 27.8 ± 6.0 in VD group was remarkably lower than 39.4 ± 4.5 in CS group (P < 0.01). The average GFAP-positive cells in the hippocampus of 31.5 ± 3.5 in VD group were not significantly lower than 37.2 ± 7.0 in CS group (P > 0.05). The expression of GFAP was detected in hippocampus and frontal cortex by western blot, however, there was no significant different expression of GFAP between VD group and CS group. (2) Neuronal apoptosis: TUNEL staining results indicated that, on postnatal day 115, fewer apoptotic cells scattered in offspring hippocampus subregion were only shown in CS group, never in VD group. No TUNEL positive staining cells were labeled in hippocampal subregion in VD group, therefore significantly lower than that of CS group (P < 0.05). There were different influences of cesarean section on GFAP expression in hippocampus or cortex in different developmental stage of offspring. Cesarean section might increase GFAP expression in the hippocampus and frontal cortex, even trigger neuronal apoptosis of hippocampus region.

Influence of mouse nerve growth factor on gliai fibrillary acidic protein expression in hippocampus of neonatal rats with hypoxic-ischemic brain damage

Objective To investigate the influence of mouse nerve growth factor (mNGF)on glial fibrillary acidic protein (GFAP) expression in hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods Sixty neonatal rats of 7 days old were randomly divided into control group (n=20) ,HIBD group (n=20) and mNGF group (n=20). After HIBD model established, mNGF of 20 ng/(g·d) was given by intramuscular injection in buttocks in mNGF group,continued five days. No intervention was given in HIBD group. 0.1mol/L PBS of 10 μ1/(g·d) was given by intramuscular injection in buttocks for the control group,continued five days. Ten rats were sacrified at 7 d and 14 d after intervention respectively in three groups, The expressions of GFAP in hippocampus were determined with immunohistochemical method. Results At 7 d and 14 d after intervention,the expression levels of GFAP in sick side hippocampous in HIBD group and mNGF group were higher than that in control group. GFAP positive cell mainly distributed in sick side hippocampal DG region in mNGF group, while CAI region in HIBD group. As compared with 7 d, the expression of GFAP in sick side hippocampus in HIBD group decreased at 14 d, while increased in mNGF group. Conclusion mNGF can increase the expression of GFAP in hippocampus of HIBD neonatal rat, and mNGF may have nervous repairing role to HIBD. Key words: Hypoxic-ischemic brain damage; Nerve growth factor; Glial fibrillary acidic protein; Neonatal rat