Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A1 receptor agonist

Lubitz, Dag K.J.E. Von; Beenhakker, Mark P.; Lin, Rick C.S.; Carter, Margaret F.; Paul, Ian A.; Bischofberger, Norbert

doi:10.1016/0014-2999(96)00101-x

Cited by 43 publications

(28 citation statements)

References 24 publications

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“…In this study, we found that, in permanent ischemia, the neuroprotective effect of CX3CL1 is lost in rats treated with DPCPX and in A 1 R Ϫ/Ϫ mice, suggesting that the involvement of A 1 R in CX3CL1-induced neuroprotection is conserved from cellular to in vivo models. This agrees with data indicating the importance of A 1 R activation in neuroprotection, reducing neuronal injury in vitro and in vivo and being involved in mechanisms of ischemic preconditioning (Von Lubitz et al, 1996;Nakamura et al, 2002). Acute A 1 R activation reduces neuronal damage, whereas A 1 R antagonists potentiate damage in neuronal cultures, brain slices, and animal models of cerebral ischemia, epileptic models, and brain trauma (Olsson et al, 2004;Cunha, 2005).…”

Section: Discussionsupporting

confidence: 90%

CX3CL1 Is Neuroprotective in Permanent Focal Cerebral Ischemia in Rodents

Cipriani¹,

Villa²,

Chece³

et al. 2011

J. Neurosci.

170

153

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The chemokine CX3CL1 and its receptor CX3CR1 are constitutively expressed in the nervous system. In this study, we used in vivo murine models of permanent middle cerebral artery occlusion (pMCAO) to investigate the protective potential of CX3CL1. We report that exogenous CX3CL1 reduced ischemia-induced cerebral infarct size, neurological deficits, and caspase-3 activation. CX3CL1-induced neuroprotective effects were long lasting, being observed up to 50 d after pMCAO in rats. The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia and, in vitro, requires the activation of adenosine receptor 1 (A 1 R). We show that, in the presence of the A 1 R antagonist 1,3-dipropyl-8-cyclopentylxanthine and in A 1 R ؊/؊ mice, the neuroprotective effect of CX3CL1 on pMCAO was abolished, indicating the critical importance of the adenosine system in CX3CL1 protection also in vivo. In apparent contrast with the above reported data but in agreement with previous findings, cx3cl1 ؊/؊ and cx3cr1 GFP/GFP mice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage in cx3cl1 ؊/؊ ischemic mice. We also report that CX3CL1 induced a different phagocytic activity in wild type and cx3cl1 ؊/؊ microglia in vitro during cotreatment with the medium conditioned by neurons damaged by oxygenglucose deprivation. Together, these data suggest that acute administration of CX3CL1 reduces ischemic damage via an adenosinedependent mechanism and that the absence of constitutive CX3CL1-CX3CR1 signaling changes the outcome of microglia-mediated effects during CX3CL1 administration to ischemic brain.

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Section: Discussionsupporting

confidence: 90%

CX3CL1 Is Neuroprotective in Permanent Focal Cerebral Ischemia in Rodents

Cipriani¹,

Villa²,

Chece³

et al. 2011

J. Neurosci.

170

153

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“…Substantial studies have shown that pre-and postischemic administration of these drugs result in a significant reduction of postischemic brain damage while A 1 receptor antagonists blocked such neuroprotection effect induced by adenosine and its analogue. [29][30][31] We hypothesized that adenosine and the adenosine A1 receptor were essential for the induction of ischemic tolerance induced by isoflurane preconditioning in the brain. The results of the present study prove that the neuroprotection induced by isoflurane pretreatment was significantly attenuated by DPCPX.…”

Section: Discussionmentioning

confidence: 99%

Neuroanesthesia and Intensive Care Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists

Liu

Xiong

Chen

et al. 2006

Can J Anesth/J Can Anesth

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Purpose:To investigate the role of the adenosine A 1 receptor in the rapid tolerance to cerebral ischemia induced by isoflurane preconditioning. Methods: Seventy-five rats were randomly assigned into five groups (n = 15 each): Control, 8-cyclopentyl-1,3-dipropulxanthine (DPCPX), Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups. All animals underwent right middle cerebral artery occlusion (MCAO) for two hours. Isoflurane preconditioning was conducted one hour before MCAO in Isoflurane, DPCPX+Isoflurane and Vehicle+Isoflurane groups by exposing the animals to 1.5% isoflurane in 98% oxygen for one hour. In the Control and DPCPX groups, animals were exposed to 98% oxygen one hour before MCAO for one hour. A selective adenosine A 1 receptor antagonist, DPCPX, was administered (0.1 mg·kg -1 ) 15 min before isoflurane/oxygen exposure in the DPCPX and DPCPX+Isoflurane groups to evaluate the effect of adenosine A 1 receptor antagonist on isoflurane preconditioning. Dimethyl sulfoxide, the solvent of DPCPX, was administered (1 mL·kg -1 ) 15 min before isoflurane exposure in the Vehicle+Isoflurane group. Neurological deficit scores and brain infarct volumes were evaluated 24 hr after reperfusion. Results: Animals in the Isoflurane and Vehicle+Isoflurane groups developed lower neurological deficit scores and smaller brain infarct volumes than the Control group (P < 0.01). Animals in the DPCPX+Isoflurane group developed higher neurological deficit scores and larger brain infarct volumes than the Isoflurane and Vehicle+Isoflurane groups (P < 0.01). Conclusion:The present study demonstrates that preconditioning with isoflurane reduces focal cerebral ischemic injury in rats, and the adenosine A 1 receptor antagonist (DPCPX) attenuates the neuroprotection induced by isoflurane preconditioning. Objectif

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“…A 1 receptor agonists have been claimed to play a pivotal role in protection from hypoxic insults (Sebastião et al, 2001). A 1 receptor activation decreases cytotoxic amino acid release from both neurons and glial cells (Schubert et al, 1994;Von Lubitz et al, 1996;Pearson et al, 2006). A 1 receptor agonists were particularly effective against cerebral ischemia (Von Lubitz et al, 1994, 1999Chen et al, 2006) and cerebral ischemia preconditioning (Heurteaux et al, 1995).…”

Section: Ischemiamentioning

confidence: 99%