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Vascular degeneration plays a significant role in contributing to neurodegenerative conditions such as Alzheimer's disease. Our understanding of the vascular components in Parkinson's disease (PD) is however limited. We have examined the vascular morphology of human brain tissue from both PD and the control cases using immunohistochemical staining and image analysis. The degenerative morphology seen in PD cases included the formation of endothelial cell "clusters," which may be contributed by the fragmentation of capillaries. When compared to the control cases, the capillaries of PDs were less in number (P < 0.001), shorter in length (P < 0.001) and larger in diameter (P < 0.01) with obvious damage to the capillary network evidenced by less branching (P < 0.001). The level of degeneration seen in the caudate nucleus was also seen in the age-matched control cases. Vessel degeneration associated with PD was, however, found in multiple brain regions, but particularly in the substantia nigra, middle frontal cortex and brain stem nuclei. The data suggest that vascular degeneration could be an additional contributing factor to the progression of PD. Thus, treatments that prevent vascular degeneration and improve vascular remodeling may be a novel target for the treatment of PD.

Background and Purpose-The fetus is well known to be able to survive prolonged exposure to asphyxia with minimal injury compared with older animals. We and others have observed a rapid suppression of EEG intensity with the onset of asphyxia, suggesting active inhibition that may be a major neuroprotective adaptation to asphyxia. Adenosine is a key regulator of cerebral metabolism in the fetus. Methods-We therefore tested the hypothesis that infusion of the specific adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), given before 10 minutes of profound asphyxia in near-term fetal sheep, would prevent neural inhibition and lead to increased brain damage. Results-DPCPX treatment was associated with a transient rise and delayed fall in EEG activity in response to cord occlusion (nϭ8) in contrast with a rapid and sustained suppression of EEG activity in controls (nϭ8). DPCPX was also associated with an earlier and greater increase in cortical impedance, reflecting earlier onset of primary cytotoxic edema, and a significantly smaller reduction in calculated cortical heat production after the start of cord occlusion. After reperfusion, DPCPX-treated fetuses but not controls developed delayed onset of seizures, which continued for 24 hours, and sustained greater selective hippocampal, striatal, and parasagittal neuronal loss after 72-hour recovery. Conclusions-These data support the hypothesis that endogenous activation of the adenosine A 1 receptor during severe asphyxia mediates the initial suppression of neural activity and is an important mechanism that protects the fetal brain.

This study was undertaken to determine the mechanisms mediating changes in fetal heart rate variability (FHRV) during and after exposure to asphyxia in the premature fetus. Preterm fetal sheep at 0.6 of gestation (91 +/- 1 days, term is 147 days) were exposed to either sham occlusion (n = 10) or to complete umbilical cord occlusion for either 20 (n = 7) or 30 min (n = 10). Cord occlusion led to a transient increase in FHRV with abrupt body movements that resolved after 5 min. In the 30 min group there was a marked increase in FHRV in the final 10 min of occlusion related to abnormal atrial activity. After reperfusion, FHRV in both study groups was initially suppressed and progressively increased to baseline levels over the first 4 h of recovery. In the 20 min group this improvement was associated with return of normal EEG activity and movements. In contrast, in the 30 min group the EEG was abnormal with epileptiform activity superimposed on a suppressed background, which was associated with abnormal fetal movements. As the epileptiform activity resolved, FHRV fell and became suppressed for the remainder of the study. Histological assessment after 72 h demonstrated severe brain stem injury in the 30 min group but not in the 20 min group. In conclusion, during early recovery from asphyxia, epileptiform activity and associated abnormal fetal movements related to evolving neural injury can cause a confounding transient increase in FHRV, which mimics the normal pattern of recovery. However, chronic suppression of FHRV was a strong predictor of severe brain stem injury.