Effects of an analogue of thyrotrophin-releasing hormone, RX77368, on infarct size and cerebral blood flow in focal cerebral ischaemia in the rat

1989 ◽  
Vol 67 (10) ◽  
pp. 1345-1350 ◽  
Author(s):  
C. T. O'Shaughnessy ◽  
N. J. Rothwell ◽  
J. Shrewsbury-Gee
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Ischaemia ◽  
Lesion Size ◽  
Focal Cerebral Ischaemia ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Stimulation Of

Effects of a stable analogue of thyrotrophin-releasing hormone, RX77368, on cerebral blood flow and infarct size have been studied in an acute model of cerebral ischaemia in the rat. Two hours after electrocoagulation of the left middle cerebral artery (MCA), the mean area of ischaemia (± SEM), determined histochemically, was 11.5 ± 2.2% of a single hemisphere and blood flow, determined using radiolabeled microspheres, was reduced by 40% in the left forebrain (p < 0.001 compared with sham-operated animals). Administration of RX77368 (50 μg/kg, intracerebroventricularly) within 10 min of arterial occlusion caused a significant (p < 0.01) reduction in mean lesion size to 3.7 ± 1.8% and stimulation of blood flow to the left ischaemic forebrain (60% above saline treated). Peripheral administration of RX77368 (1 mg/kg intraperitoneally) also significantly stimulated blood flow to the ischaemic forebrain and caused an apparent decrease in frequency of large infarcted areas of brain tissue, although mean lesion size was not significantly affected. These findings indicate that RX77368 ameliorates tissue damage in acute focal cerebral ischaemia. Such effects may be related to stimulation of cerebral blood flow.Key words: middle cerebral artery, focal cerebral ischaemia, cerebral blood flow, thyrotrophin-releasing hormone analogue.

scholarly journals Perivascular Microapplication of Endothelin-1: A New Model of Focal Cerebral Ischaemia in the Rat

1993 ◽  
Vol 13 (5) ◽  
pp. 865-871 ◽  
Author(s):  
John Sharkey
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischaemia ◽  
Dorsal Hippocampus ◽  
Focal Cerebral Ischaemia ◽  
Local Cerebral Blood Flow ◽  
Guide Cannula ◽  
Conscious Rat ◽  
Endothelin 1 ◽  
Arterial Blood

In the present study, we describe the effects of perivascular microapplication of the potent vasoconstrictor peptide endothelin-1 (Et-1; (120 pmol in 3 μl), delivered via a guide cannula stereotaxically positioned above the left cerebral artery (MCA) of the conscious male Sprague–Dawley rat. Ten minutes after the administration of Et-1, mean arterial blood pressure had increased by 20% and profound reductions in local cerebral blood flow (up to 93%) were observed within those brain areas supplied by the MCA. In addition, significant increases in local cerebral blood flow were observed within the globus pallidus (100%), substantia nigra pars reticulata (48%), ventrolateral thalamus (65%), and dorsal hippocampus (74%) ipsilateral to the insult. Twenty-four hours following the insult, the pattern of ischaemic damage was similar to that reported previously following permanent occlusion of the rat MCA. It is suggested that perivascular microapplication of Et-1 may provide a useful model for the study of the functional disturbances associated with focal cerebral ischaemia in the conscious rat.

scholarly journals Effect of 20-HETE Inhibition on Infarct Volume and Cerebral Blood Flow after Transient Middle Cerebral Artery Occlusion

2008 ◽  
Vol 29 (3) ◽  
pp. 629-639 ◽  
Author(s):  
Marija Renic ◽  
Judith A Klaus ◽  
Tomohiro Omura ◽  
Naoya Kawashima ◽  
Michihito Onishi ◽  
...  
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Dienoic Acid ◽  
Artery Occlusion ◽  
Area At Risk

This study examined the effects of an inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis, N-(3-chloro-4-morpholin-4-yl)phenyl- N'-hydroxyimido formamide (TS-011), on infarct volume, volume at risk, cerebral blood flow (CBF), and levels of cytochrome P450 (CYP450) eicosanoids in the brain after transient occlusion of the middle cerebral artery (t-MCAO) in rats. TS-011 (0.1 mg/kg, iv) reduced cortical infarct volume by approximately 70% and total infarct volume by 55%. TS-011 had no effect on the volume at risk or CBF during or up to 30 mins after the ischemic period. TS-011 reduced the delayed fall in CBF seen 2 h after reperfusion. The levels of CYP450 eicosanoids were similar in the ischemic and contralateral hemispheres after t-MCAO. TS-011 reduced 20-HETE levels in cerebral tissue by 80% but had no effect on the levels of EETs. Administration of another 20-HETE inhibitor, HET0016 (0.01 to 1.0 mg/kg, iv) or a 20-HETE antagonist 20-hydroxyeicosa-6( Z),15( Z)-dienoic acid (10 mg/kg, iv) also reduced infarct size. These results indicate that inhibitors of the synthesis or vasoconstrictor effects of 20-HETE reduce infarct size in rats after cerebral ischemia. The effects of TS-011 are not associated with changes in the area at risk or CBF and may be because of a potential protective effect in neurons subjected to ischemic stress.

scholarly journals Electrical Stimulation of Cerebellar Fastigial Nucleus Reduces Ischemic Infarction Elicited by Middle Cerebral Artery Occlusion in Rat

1991 ◽  
Vol 11 (5) ◽  
pp. 810-818 ◽  
Author(s):  
Donald J. Reis ◽  
Scott B. Berger ◽  
Mark D. Underwood ◽  
Mazen Khayata
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Electrical Stimulation ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Fastigial Nucleus ◽  
Sprague Dawley ◽  
Cholinergic Mechanism ◽  
Ischemic Infarction ◽  
Stimulation Of

Electrical stimulation of the cerebellar fastigial nucleus (FN) globally and profoundly increases cerebral blood flow via a cholinergic mechanism. In cerebral cortex, the vasodilation is unassociated with alterations in cerebral glucose utilization, a condition favoring protection against cerebral ischemia. We sought to determine whether FN stimulation would modify the size of the focal ischemic infarction resulting from occlusion of the middle cerebral artery (MCA). The MCA was occluded in anesthetized rats of the spontaneously hypertensive (SHR) or Sprague-Dawley (SD) strains with or without 1 h of electrical stimulation of the FN. Twenty-four hours later, rats were killed and the volume of the infarction established in thionin-stained sections. In SHRs, FN stimulation reduced by 40% the well-established cortical and partially subcortical infarctions elicited by occlusion of the MCA (from 186 ± 35.2 to 113 ± 47.1 mm3, mean ± SD, n = 15; p < 0.001). The zone of retrieval was anatomically constant, consisting of a rim of cortex dorsal and ventral to the infarction and medially within the thalamus and striatum corresponding to the penumbral zone described by others. The effect was comparable in rats of the SD strain having smaller infarctions. The effect of FN stimulation appears to be selective for the FN system in that it is not evoked by stimulation of the dentate nucleus and is blocked by systemic administration of atropine (1.0 mg/kg). We conclude that excitation of an intrinsic system in brain represented in the rostral FN has the capacity to reduce substantially an ischemic infarction. Whether the result is a consequence of an action of the FN upon cerebral blood flow and/or results from protective actions of released transmitter is yet unknown.

Effect of flunarizine on cerebral blood flow in baboons with or without focal cerebral ischaemia

1990 ◽  
Vol 12 (1) ◽  
pp. 60-62 ◽  
Author(s):  
Alexander Hartmann ◽  
Thomas Rommel ◽  
Roland Reddelien ◽  
Christian Dettmers ◽  
Axel Nierhaus ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischaemia ◽  
Focal Cerebral Ischaemia

scholarly journals Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion

2016 ◽  
Vol 37 (7) ◽  
pp. 2494-2508 ◽  
Author(s):  
Brad A Sutherland ◽  
Jonas C Fordsmann ◽  
Chris Martin ◽  
Ain A Neuhaus ◽  
Brent M Witgen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Cerebral Ischaemia ◽  
Neurovascular Coupling ◽  
Artery Occlusion ◽  
Ischaemia And Reperfusion ◽  
Cerebral Artery Occlusion

Hyperacute changes in cerebral blood flow during cerebral ischaemia and reperfusion are important determinants of injury. Cerebral blood flow is regulated by neurovascular coupling, and disruption of neurovascular coupling contributes to brain plasticity and repair problems. However, it is unknown how neurovascular coupling is affected hyperacutely during cerebral ischaemia and reperfusion. We have developed a remote middle cerebral artery occlusion model in the rat, which enables multi-modal assessment of neurovascular coupling immediately prior to, during and immediately following reperfusion. Male Wistar rats were subjected to remote middle cerebral artery occlusion, where a long filament was advanced intraluminally through a guide cannula in the common carotid artery. Transcallosal stimulation evoked increases in blood flow, tissue oxygenation and neuronal activity, which were diminished by middle cerebral artery occlusion and partially restored during reperfusion. These evoked responses were not affected by administration of the thrombolytic alteplase at clinically used doses. Evoked cerebral blood flow responses were fully restored at 24 h post–middle cerebral artery occlusion indicating that neurovascular dysfunction was not sustained. These data show for the first time that the rat remote middle cerebral artery occlusion model coupled with transcallosal stimulation provides a novel method for continuous assessment of hyperacute neurovascular coupling changes during ischaemia and reperfusion, and offers unique insight into hyperacute ischaemic pathophysiology.

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