Adenosine A2A receptors in early ischemic vascular injury after subarachnoid hemorrhage

Sehba, Fatima A.; Flores, Rowena; Müller, Artur; Friedrich, Victor L.; Chen, Jiang‐Fan; Britz, Gavin W.; Winn, H. Richard; Bederson, Joshua B.

doi:10.3171/2009.9.jns09802

Cited by 30 publications

(17 citation statements)

References 39 publications

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“…The effect of aSAH on parenchymal vessels appears to be comparatively greater than on large cerebral vessels (Bederson et al , 1998; Debdi et al , 1992, 1993; Sehba et al , 2010; Sehba et al , 2007b). Most of data on early vascular changes come from animal models; however, some human studies report similar findings (Bevan et al , 1998; Hatake et al , 1992; Hoelper et al , 2003; Pennings et al , 2004; Uhl et al , 2003).…”

Section: Early Events After Asahmentioning

confidence: 83%

The importance of early brain injury after subarachnoid hemorrhage

Sehba

Hou

Pluta

et al. 2012

Progress in Neurobiology

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Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts for 5% of all stroke cases. Individuals affected are typically in the prime of their lives (mean age 50 years). Approximately 12% of patients die before receiving medical attention, 33% within 48 hours and 50% within 30 days of aSAH. Of the survivors 50% suffer from permanent disability with an estimated lifetime cost more than double that of an ischemic stroke. Traditionally, spasm that develops in large cerebral arteries 3-7 days after aneurysm rupture is considered the most important determinant of brain injury and outcome after aSAH. However, recent studies show that prevention of delayed vasospasm does not improve outcome in aSAH patients. This finding has finally brought in focus the influence of early brain injury on outcome of aSAH. A substantial amount of evidence indicates that brain injury begins at the aneurysm rupture, evolves with time and plays an important role in patients’ outcome. In this manuscript we review early brain injury after aSAH. Due to the early nature, most of the information on this injury comes from animals and few only from autopsy of patients who died within days after aSAH. Consequently, we began with a review of animal models of early brain injury, next we review the mechanisms of brain injury according to the sequence of their temporal appearance and finally we discuss the failure of clinical translation of therapies successful in animal models of aSAH.

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Section: Early Events After Asahmentioning

confidence: 83%

The importance of early brain injury after subarachnoid hemorrhage

Sehba

Hou

Pluta

et al. 2012

Progress in Neurobiology

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502

392

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“…There are 4 adenosine receptor subtypes: A1AR, A2aAR, A2bAR, and A3AR [ 35 , 36 ]. Numerous authors indiscriminately select A2aAR, and Lin et al have shown that an A2aAR agonist is effective in preventing vasospasm in subarachnoid hemorrhage conditions by inhibiting eNOS expression in brain vessels and inducing iNOS expression [ 37 , 38 ]. However, in our time course experiment, A2aAR did not increase as much as A1AR after ICH.…”

Section: Discussionmentioning

confidence: 99%

A1 adenosine receptor attenuates intracerebral hemorrhage-induced secondary brain injury in rats by activating the P38-MAPKAP2-Hsp27 pathway

et al. 2016

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BackgroundThis study was designed to determine the role of the A1 adenosine receptors in intracerebral hemorrhage (ICH)-induced secondary brain injury and the underlying mechanisms.MethodsA collagenase-induced ICH model was established in Sprague–Dawley rats, and cultured primary rat cortical neurons were exposed to oxyhemoglobin at a concentration of 10 μM to mimic ICH in vitro. The A1 adenosine receptor agonist N(6)-cyclohexyladenosine and antagonist 8-phenyl-1,3-dipropylxanthine were used to study the role of A1 adenosine receptor in ICH-induced secondary brain injury, and antagonists of P38 and Hsp27 were used to study the underlying mechanisms of A1 adenosine receptor actions.ResultsThe protein level of A1 adenosine receptor was significantly increased by ICH, while there was no significant change in protein levels of the other 3 adenosine receptors. In addition, the A1 adenosine receptor expression could be increased by N(6)-cyclohexyladenosine and decreased by 8-phenyl-1,3-dipropylxanthine under ICH conditions. Activation of the A1 adenosine receptor attenuated neuronal apoptosis in the subcortex, which was associated with increased phosphorylation of P38, MAPK, MAPKAP2, and Hsp27. Inhibition of the A1 adenosine receptor resulted in opposite effects. Finally, the neuroprotective effect of the A1 adenosine receptor agonist N(6)-cyclohexyladenosine was inhibited by antagonists of P38 and Hsp27.ConclusionsThis study demonstrates that activation of the A1 adenosine receptor by N(6)-cyclohexyladenosine could prevent ICH-induced secondary brain injury via the P38-MAPKAP2-Hsp27 pathway.

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“…A 2A receptor antagonism reduced JNK MAPK activation in oligodendrocytes after cerebral ischemia (Melani et al, 2010). In A 2A receptor knockout mice there was a decrease in early ischemic vascular injury after subarachnoid hemorrhage (Sehba et al, 2010). Nearly 50% of cerebral hypoxic hyperemia was attenuated in A 2A knockout mice (Miekisiak et al, 2008).…”

Section: Ischemiamentioning

confidence: 95%