Equal contribution of increased intracranial pressure and subarachnoid blood to cerebral blood flow reduction and receptor upregulation after subarachnoid hemorrhage

Laboratory investigation

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Object

Cerebral ischemia remains the key cause of disability and death in the late phase after subarachnoid hemorrhage (SAH), and its pathogenesis is still poorly understood. The purpose of this study was to examine whether the change in intracranial pressure or the extravasated blood causes the late cerebral ischemia and the upregulation of receptors or the cerebral vasoconstriction observed following SAH.

Methods

Rats were allocated to 1 of 3 experimental conditions: 1) cisternal injection of 250 μl blood (SAH Group), 2) cisternal injection of 250 μl NaCl (Saline Group), or 3) the same procedure but without fluid injection (Sham Group). Two days after the procedure, the basilar and middle cerebral arteries were harvested, and contractile responses to endothelin (ET)–1 and 5-carboxamidotryptamine (5-CT) were investigated by means of myography. In addition, real-time polymerase chain reaction was used to determine the mRNA levels for ETA, ETB, and 5-HT1 receptors. Regional and global cerebral blood flow (CBF) were quantified by means of an autoradiographic technique.

Results

Compared with the sham condition, both SAH and saline injection resulted in significantly enhanced contraction of cerebral arteries in response to ET-1 and 5-CT. Regional and global CBF were reduced both in the Saline and SAH groups compared with the Sham Group. The mRNA levels for ETB and 5-HT1B receptors were upregulated after SAH and saline injection compared with the sham procedure. The effects in all parameters were more pronounced for SAH than for saline injection.

Conclusions

This study revealed that both the elevation of intracranial pressure and subarachnoid blood per se contribute approximately equally to the late CBF reductions and receptor upregulation following SAH.

Abbreviations used in this paper: BA = basilar artery; CBF = cerebral blood flow; ET = endothelin; ICP = intracranial pressure; MABP = mean arterial blood pressure; MCA = middle cerebral artery; PCR = polymerase chain reaction; rCBF = regional CBF; SAH = subarachnoid hemorrhage; 5-CT = 5-carboxamidotryptamine.
Article Information

Contributor Notes

Address correspondence to: Saema Ansar, Ph.D., Department of Clinical Sciences, Division of Experimental Vascular Research, BMC A13, Lund University, 221 84 Lund, Sweden. email: saema.ansar@med.lu.se.Please include this information when citing this paper: published online May 1, 2009; DOI: 10.3171/2007.3.16738.
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