epidermal-growth-factor and Cerebral-Infarction

Topics: Animals; Brain; Cerebral Infarction; Epidermal Growth Factor; Neurons; Regeneration; Stem Cells

The aim of the study was to observe the neuroreparative effect of electroacupuncture in rats with cerebral ischemia-reperfusion injury, and to explore the difference in the therapeutic effect of acupuncture on different acupoint groups after cerebral ischemia-reperfusion.. Experimental rats were randomly divided into: sham operation group, model group, electroacupuncture group, rehabilitation group, and Diankang group (electroacupuncture + rehabilitation training). There were 24 rats in each group, and the focal cerebral ischemia-reperfusion model was established by Zea-Longa suture method. After modeling, it took 4 hours to electroacupuncture at Baihui and Dazhui points, which was used to observe the changes of nerve function in rats with signs of keel nerve function defect. Protein expression was detected by immunohistochemistry.. Compared with the model group, the EA 3d, 7d, 10d groups and the rehabilitation group had no significant difference in promoting the expression of Nestin (p>0.05). There was a significant difference (p<0.01). After cerebral ischemia-reperfusion injury, the expression of bFGF and EGF on the ischemic side was stronger. The peak of bFGF expression appeared earlier, and the peak of EGF expression appeared later. The expression of bFGF and EGF in cerebral ischemic cortex at different time points of ischemia in electroacupuncture group, rehabilitation group and Diankang group was increased, and the response was enhanced. The effect of Diankang group on the upregulation of bFGF and EGF was more significant (p<0.01, p<0.05).. Under the influence of different effects, Diankang is superior to simple treatment in improving ischemic neurological dysfunction. This may be related to the fact that Diankang can promote the proliferation of neural stem cells and the expression of neurotrophic factors on the ischemic side of the rat brain.

Topics: Animals; Brain Ischemia; Cerebral Infarction; Electroacupuncture; Epidermal Growth Factor; Ischemia; Nestin; Rats; Rats, Sprague-Dawley; Reperfusion Injury

1. Studies have documented the proliferative effects of epidermal growth factor (EGF) on neural progenitor cells in the normal or injured brain. The effect of EGF on post-stroke cerebral expression of nestin, a marker of neural progenitor cells, has not been examined in hypertensive rats. 2. In the present study, adult renovascular hypertensive Sprague-Dawley rats underwent either real or sham middle cerebral artery occlusion (MCAO). Intracerebroventricular injections of either 1 microg EGF or vehicle (0.01 mol/L phosphate-buffered saline containing 0.1 mg/mL rat serum albumin) were made 24 and 48 h after MCAO. Then, 1, 2, 3 and 4 weeks after MCAO, the postural reflex was evaluated in a blinded fashion before rat brains were processed to determine the infarct volume plus immunoreactivity for nestin and/or glial fibrillary acidic protein (GFAP). Another group of rats was used to quantify nestin expression using western blot analysis. 3. Middle cerebral artery occlusion resulted in a focal infarct that was largest at 1 week and diminished gradually over the time. The impaired postural reflex followed a similar time-course. In addition, MCAO induced a marked increase in nestin expression in both hemispheres, with a higher expression in the right hemisphere; this change was maximal at 1 week and largely subsided at 3 or 4 weeks. Within the right hemisphere, nestin expression was most pronounced in the subventricular and peri-infarct zones. Most nestin-immunoreactive cells were also positive for GFAP. 4. Thus, EGF treatment significantly increases nestin expression, reduces infarct volume and ameliorates postural reflex impairment in adult hypertensive rats.

Topics: Animals; Blood Pressure; Cerebral Infarction; Drug Evaluation, Preclinical; Epidermal Growth Factor; Hypertension; Injections, Intraventricular; Intermediate Filament Proteins; Male; Mental Disorders; Nerve Tissue Proteins; Nestin; Posture; Rats; Rats, Sprague-Dawley; Reflex

To investigate the relationship of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) and proliferation of endogenous neural stem cells (NSCs) after human cerebral infarction.. Paraffin-embedded brain tissues of 22 human fatal cases of CI from the brain tissues around subventricular zone and subgranular layer zone were stained with HE and immunohistochemistry stain. The endogenous neural stem cells were marked by nestin. The expression changes of EGF, bFGF and nestin in the perihematomal tissues were analysed with the SPSS 13.0 system.. (1) Compared with the controls, the number of nestin-positive cells increased at 24 - 72 h (14 +/- 6)/HP in the ipsilateral SVZ and began to rise at 4.5 - 10 h (11 +/- 5)/HP in the ipsilateral SGZ, reached maximum at 120 - 144 h ((38 +/- 7)/HP in the SVZ, (54 +/- 17)/HP in the SGZ, and decreased markedly at 216 - 336 h, but it was still elevated compared with the controls (P < 0.05). (2) The number of bFGF-positive cells increased at 4.5 - 10 h (8.1 +/- 2.9)/HP in the SVZ, (19.0 +/- 8.2)/HP in the SGZ, reached maximum at 24 - 70 h (15.6 +/- 3.5)/HP in the SVZ, (32.0 +/- 5.7)/HP in the SGZ and decreased at 72 - 96 h, but it was still elevated compared with the controls (P < 0.05). (3) The number of EGF-positive cells increased at 4.5 - 10 h (4.3 +/- 1.6)/HP in the SVZ, (7.0 +/- 3.7)/HP in the SGZ, reached maximum at 120 - 144 h (27.0 +/- 1.4)/HP in the SVZ, (51.5 +/- 4.9)/HP in the SGZ and decreased at 216 - 336 h, but it was still elevated compared with the controls (P < 0.05).. Perhaps the increased expression of EGF and bFGF after CI was a reaction of endogenous reparation and it correlated with the proliferation and endogenous of neural stem cells in human.

Topics: Adult; Aged; Aged, 80 and over; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cerebral Infarction; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Humans; Male; Middle Aged; Multipotent Stem Cells; Neurons

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a hypoxia-inducible, neuroprotective protein that also stimulates proliferation of neuronal precursor cells. Accordingly, HB-EGF may contribute to recovery from cerebral injury through direct neuroprotective effects, by enhancing neurogenesis, or both. When administered by the intracerebroventricular route 1-3 days after focal cerebral ischemia in adult rats, HB-EGF decreased the volume of the resulting infarcts and reduced post-ischemic neurological deficits. HB-EGF also increased the incorporation of bromodeoxyuridine into cells expressing the immature neuronal marker protein TUC-4 in the dentate subgranular and rostral subventricular zones, consistent with increased proliferation of neuronal precursors. However, HB-EGF decreased the number of newborn neurons that migrated into the ischemic striatum, perhaps partly because reduction of infarct size by HB-EGF also reduced the stimulus to migration. To determine if HB-EGF might also directly inhibit migration of neuronal precursors, we co-cultured subventricular zone (SVZ) explants treated with HB-EGF or vehicle together with hypoxic cerebral cortical explants, and measured cell migration from the former toward the latter. HB-EGF reduced directed migration of SVZ cells toward the cortical explants, possibly due to a local chemoattractant effect on neuronal precursor cells, which may be mediated through the HB-EGF-specific receptor, N-arginine dibasic convertase. The delayed neuroprotective effect of HB-EGF may have implications for efforts to prolong the therapeutic window for intervention in stroke.

Topics: Animals; Brain Ischemia; Cell Division; Cell Movement; Cerebral Cortex; Cerebral Infarction; Disease Models, Animal; Epidermal Growth Factor; Heparin-binding EGF-like Growth Factor; Injections, Intraventricular; Intercellular Signaling Peptides and Proteins; Male; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley

Topics: Animals; Cell Differentiation; Cell Movement; Cell Proliferation; Cerebral Infarction; Cerebral Ventricles; Epidermal Growth Factor; Neurons; Rats; Rats, Sprague-Dawley; Stem Cells

Remodeling of the cerebral vasculature contributes to the pathogenesis of cerebral ischemia. Remodeling is caused by increased smooth muscle proliferation and may be due to an increase in the responsiveness of vascular cells to epidermal growth factor (EGF). Aldosterone is a risk factor for stroke, and the literature suggests it may play a role in increasing the expression of the receptor for EGF (EGFR). We hypothesized that mRNA for the EGF-stimulated pathway would be elevated in the vasculature of stroke-prone spontaneously hypertensive rats (SHRSP) and that this and experimental ischemic cerebral infract size would be reduced by aldosterone inhibition with spironolactone. We found that spironolactone treatment reduced the size of cerebral infarcts after middle cerebral artery occlusion in SHRSP (51.69 +/- 3.60 vs. 22.00 +/- 6.69% of hemisphere-infarcted SHRSP vs. SHRSP + spironolactone P < 0.05). Expression of EGF and EGFR mRNA was higher in cerebral vessels and aorta from adult SHRSP compared with Wistar-Kyoto rats. Only the expression of EGFR mRNA was elevated in the young SHRSP. Spironolactone reduced the EGFR mRNA expression in the aorta (1.09 +/- 0.25 vs. 0.56 +/- 0.11 phosphorimage units SHRSP vs. SHRSP + spironolactone P < 0.05) but had no effect on EGF mRNA. In vitro incubation of aorta with aldosterone +/- spironolactone produced similar results, suggesting a direct effect of aldosterone. Thus spironolactone may reduce the size of cerebral infarcts via a reduction in the expression of the EGFR mRNA, leading to reduced remodeling.

Topics: Aldosterone; Animals; Aorta; Basal Ganglia; Blood Pressure; Body Weight; Cerebral Cortex; Cerebral Infarction; Epidermal Growth Factor; ErbB Receptors; Genetic Predisposition to Disease; In Vitro Techniques; Infarction, Middle Cerebral Artery; Male; Mineralocorticoid Receptor Antagonists; Ophthalmic Artery; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Spironolactone; Stroke

Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. Neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. Magnetic resonance imaging of the brain revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This case illustrates that CADASIL can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with CADASIL closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia.

Topics: Brain; Cerebral Arterial Diseases; Cerebral Infarction; Chromosome Mapping; Chromosomes, Human, Pair 19; Cognition Disorders; Dementia, Multi-Infarct; Epidermal Growth Factor; Humans; Learning Disabilities; Leukoencephalopathy, Progressive Multifocal; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Skin

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is commonly overlooked or misdiagnosed owing to its recent identification and its variable mode of presentation. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor. To set up a diagnostic test and to delineate the Notch3 domains involved in CADASIL., we undertook mutations analysis in this gene in a group of CADASIL patients.. 50 unrelated patients with CADASIL and 100 healthy controls were screened for mutations along the entire Notch3 sequence, by means of single-strand conformation polymorphism, heteroduplex, and sequence analysis.. Strongly stereotyped mis-sense mutations, located within the epidermal-growth-factor-like (EGF-like) repeats, in the extracellular domain of Notch3, were detected in 45 patients. Clustering of mutations within the two exons encoding the first five EGF-like repeats was observed (32 patients). All these mutations lead to loss or gain of a cysteine residue and therefore to an unpaired number of cysteine residues within a given EGF domain. None of these mutations was found in the 100 controls.. Because of the strong clustering and highly stereotyped nature of the pathogenetic mutations detected in CADASIL patients, and easy and reliable diagnostic test for CADASIL is feasible. The findings suggest that aberrant dimerisation of Notch3, due to abnormal disulphide bridging with another Notch3 molecule or with another protein, may be involved in the pathogenesis of this disorder.

Topics: Case-Control Studies; Cerebral Arterial Diseases; Cerebral Infarction; DNA Mutational Analysis; Epidermal Growth Factor; Genetic Testing; Genotype; Humans; Leukoencephalopathy, Progressive Multifocal; Mutation; Proto-Oncogene Proteins; Receptor, Notch3; Receptors, Cell Surface; Receptors, Notch