Experimental Stroke Models

Hallenback, J M.

Abstract

In a focal model of brain ischemia in the spontaneously hypertensive rat (SHR), microvascular perfusion, accumulation of inflammatory mediators, and indices of cellular injury have been correlated spatially and temporally by means of multiple label immunohistochemistry in order to study their role in acute stroke. The findings clearly demonstrate that progressive impairment of microcirculation occurs in regions of brain that undergo progressive damage in the early hours of ischemia. Inhibition of tumor necrosis factor-alpha (TNF-alpha) with TNF-binding protein reduces brain infarct volume in middle cerebral artery occlusion (MCAO) models in the rat and mouse. In addition, TNF-binding protein attenuates the progressive impairment of microvascular perfusion that occurs during the early hours of focal brain ischemia. These findings implicate TNF-alpha as a mediator of progressive brain damage during acute stroke. Lipopolysaccharide (LPS) pretreatment has been demonstrated to induce tolerance to focal brain ischemia in the MCAO model in the SHR. TNF binding protein blocks this tolerance implicating TNF-alpha as the mediator. One feature of this form of tolerance is that the degree of microcirculatory perfusion impairment in brain is reduced.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Neurological Disorders and Stroke (NINDS)
• Type: Intramural Research (Z01)
• Project #: 1Z01NS002924-02
• Application #: 6163110
• Study Section: Surgery and Bioengineering Study Section (SB)
• Support Year: 2
• Fiscal Year: 1997

Institution

• Name: National Institute of Neurological Disorders and Stroke
• Country: United States

Publications

Mou, Yongshan; Wilgenburg, Brian J; Lee, Yang-ja et al. (2013) A method for hypothermia-induction and maintenance allows precise body and brain temperature control in mice. J Neurosci Methods 213:1-5

Batra, Ayush; Latour, Lawrence L; Ruetzler, Christl A et al. (2010) Increased plasma and tissue MMP levels are associated with BCSFB and BBB disruption evident on post-contrast FLAIR after experimental stroke. J Cereb Blood Flow Metab 30:1188-99

Nakayama, Toshiyuki; Illoh, Kachikwu; Ruetzler, Christl et al. (2007) Intranasal administration of E-selectin to induce immunological tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis. Brain Res 1132:177-84

Hallenbeck, John (2007) Adaptive Immunity: Introduction. Stroke 38:768-769

Hallenbeck, John; Del Zoppo, Gregory; Jacobs, Tom et al. (2006) Immunomodulation strategies for preventing vascular disease of the brain and heart: workshop summary. Stroke 37:3035-42

Chamorro, Angel; Hallenbeck, John (2006) The harms and benefits of inflammatory and immune responses in vascular disease. Stroke 37:291-3

Illoh, Kachi; Campbell, Catherine; Illoh, Orieji et al. (2006) Mucosal tolerance to E-selectin and response to systemic inflammation. J Cereb Blood Flow Metab 26:1538-50

Chen, Yun; Samal, Babru; Hamelink, Carol R et al. (2006) Neuroprotection by endogenous and exogenous PACAP following stroke. Regul Pept 137:4-19

Hallenbeck, John M; Hansson, Goran K; Becker, Kyra J (2005) Immunology of ischemic vascular disease: plaque to attack. Trends Immunol 26:550-6

Hillion, Joelle A; Takahashi, Kenzo; Maric, Dragan et al. (2005) Development of an ischemic tolerance model in a PC12 cell line. J Cereb Blood Flow Metab 25:154-62