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Angiotensin receptor type 2 activation induces neuroprotection and neurogenesis after traumatic brain injury.


ABSTRACT: Angiotensin II receptor type 2 (AT(2)) agonists have been shown to limit brain ischemic insult and to improve its outcome. The activation of AT(2) was also linked to induced neuronal proliferation and differentiation in vitro. In this study, we examined the therapeutic potential of AT(2) activation following traumatic brain injury (TBI) in mice, a brain pathology that displays ischemia-like secondary damages. The AT(2) agonist CGP42112A was continuously infused immediately after closed head injury (CHI) for 3 days. We have followed the functional recovery of the injured mice for 35 days post-CHI, and evaluated cognitive function, lesion volume, molecular signaling, and neurogenesis at different time points after the impact. We found dose-dependent improvement in functional recovery and cognitive performance after CGP42112A treatment that was accompanied by reduced lesion volume and induced neurogenesis in the neurogenic niches of the brain and also in the injury region. At the cellular/molecular level, CGP42112A induced early activation of neuroprotective kinases protein kinase B (Akt) and extracellular-regulated kinases ½ (ERK½), and the neurotrophins nerve growth factor and brain-derived neurotrophic factor; all were blocked by treatment with the AT(2) antagonist PD123319. Our results suggest that AT(2) activation after TBI promotes neuroprotection and neurogenesis, and may be a novel approach for the development of new drugs to treat victims of TBI.

SUBMITTER: Umschweif G 

PROVIDER: S-EPMC4121449 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Angiotensin receptor type 2 activation induces neuroprotection and neurogenesis after traumatic brain injury.

Umschweif Gali G   Liraz-Zaltsman Sigal S   Shabashov Dalia D   Alexandrovich Alexander A   Trembovler Victoria V   Horowitz Michal M   Shohami Esther E  

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20140701 3


Angiotensin II receptor type 2 (AT(2)) agonists have been shown to limit brain ischemic insult and to improve its outcome. The activation of AT(2) was also linked to induced neuronal proliferation and differentiation in vitro. In this study, we examined the therapeutic potential of AT(2) activation following traumatic brain injury (TBI) in mice, a brain pathology that displays ischemia-like secondary damages. The AT(2) agonist CGP42112A was continuously infused immediately after closed head inju  ...[more]

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