In support of these views, experimental evidence has been acquired on the enlargement of the arteries at the base of the brain.The initial arterial dilation is probably flowinduced, involving the activation of nitric oxide synthase, NADPH oxidase, and phosphatidylinositol kinase. Furthermore, vascular remodeling and arteriogenesis take place, as indicated by the appearance of extracranial collaterals emanating from the vertebral arteries and by the tortuosity of the basilar and vertebral arteries. At the level of the microvessels, the specific compensatory mechanisms are still uncertain.Nitric oxide is a very potent vasodilator, which is released at increased concentration in the brain parenchyma in response to cerebral ischemic insults.The accumulation of collagen fibers in the microvascular basement membrane may hinder specific BBB transport for important nutrients such as glucose and essential amino acids and could hamper the fine regulation of the regional CBF. In the aging brain, a significant correlation has been established between collagen deposits in the microvascular wall and advancing age in the frontal and occipital WM. Furthermore, in AD, the proportion of capillaries displaying collagen accumulation in the microvascular basement membrane in the cingulate cortex was considerably higher than in agematched controls. Whether such basement membrane pathology is related to cerebral hypoperfusion has been tested in the VO model.Electron microscopic examination revealed microvascular basement membrane thickening and collagen deposits comparable to those seen in the human post mortem studies after months of VO.The proportion of affected capillaries in the hippocampus in VO rats almost doubled as compared with controls. A similar analysis did not demonstrate significant basement membrane pathology weeks after VO onset not subjected to any surgical intervention also displayed marked capillary basement membrane pathology, chronic cerebral hypoperfusion is suggested to be a causative, accelerating condition for such agerelated BBB damage.In conclusion, the condition of the BBB in VO rats appears to correspond closely to microvascular damage in the human.While breaching of the BBB in human conditions or experimental cerebral hypoperfusion cannot be clearly proven, the capillary basement membrane pathology in the VO model is very similar to the situation in human aging and dementia.Between and min after the onset of VO, the evoked population spike amplitudes decreased dramatically and became undetectable.However, this functional impairment proved to be Targetmol’s Carbamazepine reversible.When the experiment was performed days after the induction of VO, the evoked population spikes no longer differed from those in the shamoperated controls. The explanation for this surprising recovery is twofold: first, the silencing of the CA pyramidal cells was not followed by immediate neuronal cell death, but possibly by metabolic adaptation; and second, the blood flow to the hippocampus has been shown to start recovering already on the second day after occlusion of the vessels, which may contribute to the returning functional activity of the pyramidal cells.It would be interesting to repeat the experiment at a later time, when hippocampal neuronal cell death is obvious.In another experimental approach, the electroencephalogram was recorded in rats in the acute phase of VO.In half of the animals, slow waves with reduced amplitudes appeared initially in the EEG, the rhythm of the EEG then gradually disappeared, and finally, safter the induction of VO, the EEG became isoelectric.