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

2009 ◽  
Vol 111 (5) ◽  
pp. 978-987 ◽  
Author(s):  
Saema Ansar ◽  
Lars Edvinsson
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Intracranial Pressure ◽  
Sham Group ◽  
Cerebral Arteries ◽  
Mrna Levels ◽  
Saline Injection ◽  
Receptor Upregulation ◽  
Subarachnoid Blood

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.

Neurokinin-1 receptor antagonism in a rat model of subarachnoid hemorrhage: prevention of upregulation of contractile ETB and 5-HT1B receptors and cerebral blood flow reduction

2007 ◽  
Vol 106 (5) ◽  
pp. 881-886 ◽  
Author(s):  
Saema Ansar ◽  
Niels-Aage Svendgaard ◽  
Lars Edvinsson
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Receptor Agonist ◽  
Cerebral Arteries ◽  
Basilar Arteries ◽  
Receptor Upregulation ◽  
Neurokinin 1 ◽  
Autoradiographic Technique ◽  
Vascular Receptor

Object Cerebral vasospasm following subarachnoid hemorrhage (SAH) leads to reduced cerebral blood flow (CBF) and to cerebral ischemia, in some cases even producing infarction and long-term disability. The goal of the present study was to investigate the hypothesis that inhibition of neurokinin-1 receptors (NK1Rs) by administration of L-822429 blunts the decrease in CBF as well as cerebrovascular receptor upregulation in an animal model of SAH. Methods Subarachnoid hemorrhage was induced in rats by injection of 250 μl of blood into the prechiasmatic cistern. The NK1R inhibitor L-822429 was injected intracisternally 30 minutes and 24 hours after the induction of SAH. Two days after SAH induction, the basilar arteries were harvested, and contractile responses to endothelin-1 (ET-1, an ETA- and ETB-receptor agonist) and 5-carboxamidotryptamine (a 5-hydroxytryptamine-1 [5-HT1]-receptor agonist) were investigated using sensitive myographs. To determine whether NK1R inhibition had an influence on local CBF after post-SAH, a quantitative autoradiographic technique was used. After SAH, the vascular receptor phenotype was changed in cerebral arteries through upregulation of contractile ETB and 5-HT1B receptors, while regional and total CBF were markedly reduced. Treatment with the selective NK1R inhibitor L-822429 prevented both the receptor upregulation and the reduction in regional and global CBF. Conclusions The data reveal the coregulation of vascular receptor changes and blood flow effects, and also show that interaction with a small-molecule NK1R antagonist is a promising area of focus for the development of specific treatments for SAH.

scholarly journals Blockade of the MEK/ERK Pathway with a Raf Inhibitor Prevents Activation of Pro-Inflammatory Mediators in Cerebral Arteries and Reduction in Cerebral Blood Flow after Subarachnoid Hemorrhage in a Rat Model

2010 ◽  
Vol 31 (1) ◽  
pp. 144-154 ◽  
Author(s):  
Aida Maddahi ◽  
Saema Ansar ◽  
Qingwen Chen ◽  
Lars Edvinsson
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Rat Model ◽  
Inflammatory Mediators ◽  
Cerebral Arteries ◽  
High Morbidity ◽  
Mrna Levels ◽  
Erk Pathway

Cerebral ischemia that develops after subarachnoid hemorrhage (SAH) carries high morbidity and mortality. Inflammatory mediators are involved in the development of cerebral ischemia through activation of the mitogen-activated protein kinase pathway. We hypothesized that blockade of the MAPkinase/ERK (MEK)/extracellular signal-regulated kinase (ERK) pathway upstream with a specific raf inhibitor would prevent SAH-induced activation of the cerebrovascular inflammatory response. The raf inhibitor SB-386023-b was injected intracisternally in our rat model at 0, 6, or 12 hours after the SAH. After 48 hours, cerebral arteries were harvested, and iNOS, interleukin (IL)-6, IL-1β, matrix metalloproteinase (MMP)-9, tissue inhibitors of metalloproteinase (TIMP)-1, and phosphorylated ERK1/2 were investigated by immunofluorescence, real-time polymerase chain reaction (PCR), and Western blot analysis. Cerebral blood flow (CBF) was measured using autoradiography. Protein levels of MMP-9, TIMP-1, iNOS, IL-6, and IL-1β were increased after SAH, as were mRNA levels of IL-6, MMP-9, and TIMP-1. After SAH, pERK1/2 was increased, but CBF was reduced. Treatment with SB-386023-b at 0 or 6 hours after SAH normalized CBF and prevented SAH-induced upregulation of MMPs, pro-inflammatory cytokines, and pERK1/2 proteins. These results suggested that inhibition of MEK/ERK signal transduction by a specific raf inhibitor administered up to 6 hours after SAH normalized the expression of pro-inflammatory mediators and extracellular matrix-related genes.

scholarly journals Changes of Intracranial Pressure and Cerebral Blood Flow in Patients with Normal Pressure Hydrocephalus after Subarachnoid Hemorrhage

1981 ◽  
Vol 21 (4) ◽  
pp. 379-388 ◽  
Author(s):  
MINORU HAYASHI ◽  
HIDENORI KOBAYASHI ◽  
SHIGERU MUNEMOTO ◽  
SOTARO HIGASHI ◽  
JUN-ICHI NOZAKI ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Intracranial Pressure ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure

scholarly journals Concentrations of estradiol, progesterone and testosterone in sefrum and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage correlate weakly with transcranial Doppler flow velocities

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jan Martin ◽  
Eva Plank ◽  
Bernhard Ulm ◽  
Jens Gempt ◽  
Maria Wostrack ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Transcranial Doppler ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Blood Flow Velocities ◽  
Flow Velocities

Abstract Background The implication of the steroids estradiol, progesterone and testosterone in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) has not been comprehensively assessed. In rodents, studies suggested beneficial effects of steroids on cerebral vasospasm after experimental SAH. Studies in humans are warranted, however, a general dilemma of human studies on neuroactive substances is that the brain is not directly accessible and that concentrations in the periphery may not adequately parallel concentrations in the central compartments. In the present study, concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid (CSF) of patients with aSAH were determined. Blood flow velocities in cerebral arteries were measured by transcranial Doppler sonography (TCD). The aim of this study was to evaluate the correlations between the cerebral blood flow velocities and levels of estradiol, progesterone and testosterone in CSF and serum. Results Samples of serum and CSF of 42 patients with aSAH were collected concomitantly daily or every other day via the arterial line and the external ventricular drainage for two weeks after the hemorrhage. Blood flow velocities in the cerebral arteries were determined by TCD. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. The correlation analysis revealed very weak correlations between cerebral blood flow velocities and concentrations of estradiol, progesterone and testosterone levels in both compartments with correlation coefficients below 0.2. Conclusions In humans with aSAH, merely very weak correlations between flow velocities in cerebral arteries and concentrations of estradiol, progesterone and testosterone in serum and CSF were demonstrated. These results suggest a limited influence of the respective steroids on cerebral vascular tone although vasodilatory effects were described in rodent studies. Thus, the implication of steroids in processes of neurological deterioration warrants further clarification.

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