Reduction In Glial Fibrillary Acidic Protein Research Articles

Hydrogen sulphide protects mice against the mutual aggravation of cerebral ischaemia/reperfusion injury and colitis

This study was undertaken to determine whether ischaemia/reperfusion (I/R)-induced brain injury and dextran sulfate sodium (DSS)-induced colitis in mice are related. A cerebral I/R model of mice was established by blocking the bilateral common carotid arteries; 3% DSS in drinking water was administered to mice for 7 days to induce colitis; mice with cerebral I/R and colitis were administered DSS for 7 days from the third day onwards after acute cerebral I/R. Brain damage and intestinal inflammation were also tested. The results revealed that cerebral I/R induced brain damage and a marked increase in glial fibrillary acidic protein (GFAP) expression and upregulation of Rho-associated coiled coil-forming protein kinase (RhoA/ROCK) pathway in mouse hippocampal tissues. However, in the colon tissues of mice with colitis, we found a reduction in GFAP. In addition, the expression of endogenous hydrogen sulphide (H2S) synthase reduced in mice brain tissues with cerebral I/R injury, as well.as in mouse colon tissues with colitis. Interestingly, the cerebral I/R-induced pathological changes in mouse brain tissues were aggravated by colitis, colitis mediated colon inflammation, and pathological changes in intestinal tissues had deteriorated when the mice suffered cerebral I/R 2 days before DSS administration. However, brain injury and colon inflammation in mice suffering from both cerebral I/R and colitis were ameliorated by NaHS, an exogenous H2S donor. Furthermore, we found that NaHS promoted the transformation of astrocytes from “A1” to “A2” type. These findings reveal that cerebral I/R injury and colitis are related, the mechanism is correlated with endogenous H2S deficiency.

Alleviation of Cerebral Infarction of Rats With Middle Cerebral Artery Occlusion by Inhibition of Aquaporin 4 in the Supraoptic Nucleus.

In ischemic stroke, vasopressin hypersecretion is a critical factor of cerebral swelling and brain injury. To clarify neural mechanisms underlying ischemic stroke-evoked vasopressin hypersecretion, we observed the effect of unilateral permanent middle cerebral artery occlusion (MCAO) in rats on astrocytic plasticity and vasopressin neuronal activity in the supraoptic nucleus (SON) as well as their associated cerebral injuries. MCAO for 8 hr caused cerebral infarction in the MCAO side where water contents also increased. Immunohistochemical examination revealed that the percentage of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2)-positive vasopressin neurons in the SON of MCAO side was significantly higher than that in non-MCAO side and in sham group. In the cortex, pERK1/2 and aquaporin 4 expressions increased significantly in the infarction area, while glial fibrillary acidic protein (GFAP) reduced significantly compared with the noninfarction side in brain cortex. Microinjection of N-(1,3,4-Thiadiazolyl)nicotinamide-020 [TGN-020, a specific blocker of aquaporin 4] into the SON blocked MCAO-evoked increases in pERK1/2 in the SON as well as the reduction of GFAP and the increase in pERK1/2 and aquaporin 4 in the infarction area of the cortex. Finally, oxygen and glucose deprivation reduced GFAP expression and the colocalization and molecular association of GFAP with aquaporin 4 in the SON in brain slices. These effects were blocked by TGN-020 and/or phloretin, a blocker of astrocytic volume-regulated anion channels. These findings indicate that blocking aquaporin 4 in the SON may reduce the activation of vasopressin neurons and brain injuries elicited by vasopressin during ischemic stroke.

A morphometric study of glia and neurons in the anterior cingulate cortex in mood disorder

The anterior cingulate cortex (ACC) is a key region for the pathophysiology and treatment of depression. However, it remains unclear whether and how the morphology of the ACC is altered in subjects with mood disorders. A post mortem morphometric study of the supragenual ACC (Brodmann area 24b) in seven subjects with mood disorder and nine comparison subjects. We measured glial and neuronal density, and neuronal size and shape. We also quantified the astrocytic marker, glial fibrillary acidic protein (GFAP), using immunoautoradiography. Cortical and layer thickness did not differ between groups. Subjects with mood disorder had a decreased density of glial cells across all layers, and a reduction in GFAP in white matter. The density of pyramidal neurons was decreased selectively in layer Vb, and their size was increased in layers V and VI. The shape of pyramidal neurons also differed in mood disorder, in layers Va and VI. These data provide further evidence for morphometric alterations in glia and pyramidal neurons in mood disorder. They represent a possible cellular basis for the aberrant functioning and connectivity of the ACC apparent from neuroimaging and other studies.

Effects of diabetes on expression of glial fibrillary acidic protein and neurotrophins in rat colon

Diabetes can result in loss of enteric neurons and subsequent gastrointestinal complications, but the influence of diabetes on the expression of glial fibrillary acidic protein (GFAP) and neurotrophins in gut remains unknown. The aim of this study was to determine the changes of GFAP and neurotrophins in the colon of diabetic rats. The distribution of the glial marker-GFAP was explored by immunofluorescence histochemistry and western blot in colons of streptozotocin (STZ)-diabetic and age-matched control rats. And the expression of glia cell-derived neurotrophic factor (GDNF), neurotrophin 3 (NT-3) and nerve growth factor (NGF) was analyzed by real-time PCR and western blot. Studies were carried out at 4 and 12 weeks of diabetes duration. Immunostaining and western blot showed diabetes induced a decrease in the intensity of staining of GFAP positive enteric glial cells (EGCs) and GFAP protein levels at 4 weeks and attenuated GFAP expression was more evident at 12 weeks. Moreover, mRNA and protein analysis indicated that the levels of GDNF, NT-3 and NGF were down-regulated in diabetic rats. These findings suggest that the induction of diabetes is associated with a reduction in GFAP and neurotrophins expression in the colon, which may affect the role of EGCs and neurotrophins in the enteric plexus. This in turn may partly contribute to the physiopathologic changes associated with diabetic state in the gastrointestinal tract.

Reduction of GFAP induced by long dark rearing is not restricted to visual cortex

A key component of the astrocyte cytoskeleton is the glial fibrillary acidic protein (GFAP), which plays an essential role in neuron/astrocyte interactions. Environmental conditioning, such as visual experience manipulation, can affect neuronal and/or glial plasticity in specific brain areas. Previous work from our laboratory showed that short light deprivation throughout the period of GFAP maturation does not influence the expression profile of GFAP in mouse visual cortex; however, it was strong enough to affect neuronal phenotype. It was suggested that visual experience controls the maturation of the neuronal circuitry in this brain area. Therefore, to see whether the modifications of neuronal activity induced by light deprivation affect the maintenance of normal astrocytic phenotype, the dark rearing protocol was extended until the adult life. GFAP-immunoreactive cells were dramatically affected, showing an 80% decrease in number. In addition, GFAP protein level exhibited a 50% reduction, while its mRNA remained unaffected. Besides the visual cortex, two other areas of the brain not directly involved in vision, the hippocampus and the motor cortex, were chosen as internal controls. Unexpectedly, also in these areas, astrocytes were affected by light deprivation. The present results show that lack of visual experience for long periods of time deeply affects glial phenotype not only in visual areas but also in brain regions not directly involved in sensory processing.

Repeated prenatal corticosteroids reduce glial fibrillary acidic protein in the ovine central nervous system.

A single course of corticosteroid reduces intracranial hemorrhage in preterm infants. The mechanism of protection is unclear. Glial fibrillary acidic protein (GFAP), expressed by astrocytes, is regulated by glucosteroids and is an important component of the cells forming the blood brain barrier. We have evaluated the effect of prenatal corticosteroid upon ovine GFAP. Date-mated ewes were studied in two protocols and lambs delivered on day 125 or 145 (term = 150). In the maternal injection protocol (n = 36) ewes were administered saline, single or repeated injections of corticosteroid. In the fetal injection protocol (n = 48) direct ultrasound-guided fetal injections of saline, single or repeated corticosteroid were administered, and an additional control group did not receive fetal injections. Optic nerve GFAP immunohistochemistry was performed and quantified. At 125 days, repeated, but not single, administration of corticosteroid, by either maternal or fetal route, was associated with a significant reduction in GFAP (both p < 0.002); by 145 days, the deficit had recovered (both p > 0.05). The process of performing repeated fetal injections had an independent effect upon GFAP at 145 days (p = 0.002). Repeated administration of corticosteroid results in a reduction in GFAP in the developing ovine optic nerve, with recovery demonstrated by 145 days.