String Vessel Formation is Increased in the Brain of Parkinson Disease.

BACKGROUND: String vessels are collapsed basement membrane without endothelium and have no function in circulation. String vessel formation contributes to vascular degeneration in Alzheimer disease. By comparing to age-matched control cases we have recently reported endothelial degeneration in brain capillaries of human Parkinson disease (PD). OBJECTIVE: Current study evaluated changes of basement membrane of capillaries, string vessel formation and their association with astrocytes, blood-brain-barrier integrity and neuronal degeneration in PD. METHODS: Brain tissue from human cases of PD and age-matched controls was used. Immunohistochemical staining for collagen IV, GFAP, NeuN, tyrosine hydroxylase, fibrinogen and Factor VIII was evaluated by image analysis in the substantia nigra, caudate nucleus and middle frontal gyrus. RESULTS: While the basement-membrane-associated vessel density was similar between the two groups, the density of string vessels was significantly increased in the PD cases, particularly in the substantia nigra. Neuronal degeneration was found in all brain regions. Astrocytes and fibrinogen were increased in the caudate nuclei of PD cases compared with control cases. CONCLUSIONS: Endothelial degeneration and preservation of basement membrane result in an increase of string vessel formation in PD. The data may suggest a possible role for cerebral hypoperfusion in the neuronal degeneration characteristic of PD, which needs further investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be associated with disruption of the blood-brain barrier in this brain region.

Vascular degeneration in Parkinson's disease.

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.