Herpes-simplex virus encephalitis is characterized by an early MMP-9 increase and collagen type IV degradation

Sellner, Johann; Simon, Franziska; Meyding-Lamade, Uta; Leib, Stephen L. (2006). Herpes-simplex virus encephalitis is characterized by an early MMP-9 increase and collagen type IV degradation. Brain research, 1125(1), pp. 155-162. Amsterdam: Elsevier 10.1016/j.brainres.2006.09.093

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Cerebrovascular complications including cerebral edema, raised intracranial pressure and hemorrhage contribute to the high mortality and morbidity of herpes-simplex virus encephalitis (HSE). We examined changes of collagen type IV, the major constituent of the neurovascular matrix, together with expression and localization of matrix-degrading enzymes during the development of acute HSE. In an experimental model of focal HSE, we found that early, symptomatic HSE (3 days after infection) and acute, fully developed HSE (7 days after infection) are associated with significantly raised levels of matrix-metalloproteinase-9 (MMP-9) (both P<0.05). In situ zymography of brain sections revealed that the increase of MMP-9 was restricted to the cerebral vasculature in early HSE and further expanded towards the perivascular space and adjacent tissue in acute HSE. Around the cerebral vasculature, we observed that MMP-9 activity was insufficiently counterbalanced by its endogenous tissue inhibitor of MMP (TIMP) TIMP-1, resulting in loss of collagen type IV. Our findings suggest that MMP-9 is involved in the evolution of HSE by causing damage to the cerebral vasculature. The degradation of the neurovascular matrix in HSE facilitates the development of cerebrovascular complications and may represent a target for novel adjuvant treatment strategies.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology 04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
UniBE Contributor:	Sellner, Johann, Leib, Stephen
ISSN:	0006-8993
ISBN:	17109833
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:46
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1016/j.brainres.2006.09.093
PubMed ID:	17109833
Web of Science ID:	000243251200018
URI:	https://boris.unibe.ch/id/eprint/19104 (FactScience: 1475)