Tags

Type your tag names separated by a space and hit enter

Neuroserpin, a neuroprotective factor in focal ischemic stroke.
Mol Cell Neurosci. 2001 Nov; 18(5):443-57.MC

Abstract

Because recent studies have indicated that tissue plasminogen activator (tPA) aggravates neurodegenerative processes in many neural pathologies, we studied whether the endogenous tPA antagonist neuroserpin has a neuroprotective effect in an animal model of focal ischemic stroke. After induction of a focal ischemic stroke in the mouse by occlusion of the middle cerebral artery, we found that microglial cells accumulated in the marginal zone of the infarct are the most important source for both plasminogen activators, tPA and uPA. To investigate the effect of neuroserpin on the size and the histology of the infarct we produced transgenic mice overexpressing neuroserpin approximately sixfold in the nervous system. In the brain of these mice the total tPA activity in the uninjured tissue was strongly reduced. After induction of a focal ischemic stroke in the transgenic mice by a permanent occlusion of the middle cerebral artery (MCA), the infarcts were 30% smaller than in the wild-type mice. Immunohistochemical analyses and in situ hybridization revealed an attenuation of the microglial activation in the reactive zone. Concomitantly, the microglial production of tPA and uPA, as well as the PA-activity in the infarct region was markedly reduced. Thus, our results indicate that neuroserpin reduces microglial activation and, therefore, the PA activity and has a neuroprotective role after focal ischemic stroke.

Authors+Show Affiliations

Institute of Biochemistry, University of Zurich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11922137

Citation

Cinelli, P, et al. "Neuroserpin, a Neuroprotective Factor in Focal Ischemic Stroke." Molecular and Cellular Neurosciences, vol. 18, no. 5, 2001, pp. 443-57.
Cinelli P, Madani R, Tsuzuki N, et al. Neuroserpin, a neuroprotective factor in focal ischemic stroke. Mol Cell Neurosci. 2001;18(5):443-57.
Cinelli, P., Madani, R., Tsuzuki, N., Vallet, P., Arras, M., Zhao, C. N., Osterwalder, T., Rülicke, T., & Sonderegger, P. (2001). Neuroserpin, a neuroprotective factor in focal ischemic stroke. Molecular and Cellular Neurosciences, 18(5), 443-57.
Cinelli P, et al. Neuroserpin, a Neuroprotective Factor in Focal Ischemic Stroke. Mol Cell Neurosci. 2001;18(5):443-57. PubMed PMID: 11922137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroserpin, a neuroprotective factor in focal ischemic stroke. AU - Cinelli,P, AU - Madani,R, AU - Tsuzuki,N, AU - Vallet,P, AU - Arras,M, AU - Zhao,C N, AU - Osterwalder,T, AU - Rülicke,T, AU - Sonderegger,P, PY - 2002/4/2/pubmed PY - 2002/5/23/medline PY - 2002/4/2/entrez SP - 443 EP - 57 JF - Molecular and cellular neurosciences JO - Mol Cell Neurosci VL - 18 IS - 5 N2 - Because recent studies have indicated that tissue plasminogen activator (tPA) aggravates neurodegenerative processes in many neural pathologies, we studied whether the endogenous tPA antagonist neuroserpin has a neuroprotective effect in an animal model of focal ischemic stroke. After induction of a focal ischemic stroke in the mouse by occlusion of the middle cerebral artery, we found that microglial cells accumulated in the marginal zone of the infarct are the most important source for both plasminogen activators, tPA and uPA. To investigate the effect of neuroserpin on the size and the histology of the infarct we produced transgenic mice overexpressing neuroserpin approximately sixfold in the nervous system. In the brain of these mice the total tPA activity in the uninjured tissue was strongly reduced. After induction of a focal ischemic stroke in the transgenic mice by a permanent occlusion of the middle cerebral artery (MCA), the infarcts were 30% smaller than in the wild-type mice. Immunohistochemical analyses and in situ hybridization revealed an attenuation of the microglial activation in the reactive zone. Concomitantly, the microglial production of tPA and uPA, as well as the PA-activity in the infarct region was markedly reduced. Thus, our results indicate that neuroserpin reduces microglial activation and, therefore, the PA activity and has a neuroprotective role after focal ischemic stroke. SN - 1044-7431 UR - https://www.unboundmedicine.com/medline/citation/11922137/Neuroserpin_a_neuroprotective_factor_in_focal_ischemic_stroke_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1044-7431(01)91028-0 DB - PRIME DP - Unbound Medicine ER -