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

O’Shaughnessy, Celestine T.; Rothwell, Nancy J.; Shrewsbury-Gee, J.

doi:10.1139/y89-214

Cited by 13 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A TRH analogue (RX77368) with a longer duration of action, was given intracerebroventricularly to anaesthetized rats with a middle cerebral artery occlusion. The blood flow increased to the ischaemic areas in the forebrain and a significantly reduced size of the ischaemic lesion was foundafterRX77368 compared to saline administration (22).…”

Section: Discussionmentioning

confidence: 92%

Effects of thyrotropin-releasing hormone on regional cerebral blood flow in man

Oturai

Friberg

Sam

et al. 1992

Acta Endocrinologica

View full text Add to dashboard Cite

of thyrotropin-releasing hormone on regional cerebral blood flow in man. Acta Endocrinol 1992:126:243-6. To assess the regional changes in cerebral blood flow, 10 healthy volunteers were given 400 \ g=m\ g thyrotropin-releasing hormone iv in a double-blind, randomized, cross-over study. Regional cerebral blood flow was determined simultaneously in two slices of the brain, using a single photon emission computerized tomograph and inhalation of 1 33Xe. Thyrotropin-releasing hormone caused a significant mean increase of 3.7% (range \m=-\8.8\p=n-\22.7)in blood flow in a region consistent with the left thalamus compared to placebo (3.2% decrease). In 25 other regions no significant change was detected. The thalamic region has previously been shown to be a region especially affected by thyrotropin-releasing hormone in animal studies. The thyrotropin-releasing hormone injection was followed by a minor rise in systemic blood pressure, but not a rise that could affect the cerebral blood flow. The effect of thyrotropin-releasing hormone on the regional cerebral blood flow in the thalamic region was much lower compared to changes found in sedated animals given a hundredfold higher dose of thyrotropin\x=req-\ releasing hormone.TRH and its receptors have been demonstrated in several regions of the central nervous system (CNS), as well as in organs outside the CNS (1-4). TRH stimulates the release of thyrotropin from the pituitary, but several other physiological effects of TRH have been described (3, 5, 6), leading to the assumption that TRH might act as a neuromodulator or a neurotransmitter.In sedated rabbits, cats and rats TRH causes a considerable cerebral vasodilatation (7-9). However, the TRH effect on the cerebral blood flow has been studied mainly in animal models. This is the first report on the effect of TRH on the human regional cerebral blood flow (rCBF) in healthy adults. Material and methodsTen healthy, male volunteers, median age 27 years (range 23-30) were examined in a double-blind, ran¬ domized, cross-over study after informed consent had been obtained. rCBF was measured on two days separ¬ ated by an interval of 14 days. It was measured 30 min before and 5 min after the iv administration of 400 yg TRH (Protirelinum®), or placebo (0.9% saline). rCBF measurements were carried out with the 133Xe inhalation technique using a fast rotating, brain dedi¬ cated single photon emission computerized tomograph, SPECT (Tomomatic 232). The li3Xe uptake and clear¬ ance in two slices (each 17 mm thick) of the brain (Fig. 1 ) were recorded for 4.5 min (10). The slices were pos¬ itioned above and parallel to a line connecting the lateral canthus of the orbital cavity with the centre of the external acoustic meatus-the OM line. The lowest slice level was OM-f-30 mm, containing the thalamus and other inferiorly located brain structures. Thus, the upper slice level was automatically obtaining information from the slice level OM + 70 mm. The spatial resolution in the transversal plane was 12 mm.The areas where the highest increm...

show abstract

Section: Discussionmentioning

confidence: 92%

Effects of thyrotropin-releasing hormone on regional cerebral blood flow in man

Oturai

Friberg

Sam

et al. 1992

Acta Endocrinologica

View full text Add to dashboard Cite

show abstract

“…It has been reported that the mechanism responsible for increased local CBF by TRH 22–24 may result from its cholinergic 25 or prostaglandin‐mediated vasodilator action 26 . O’Shaughnessy et al have reported that a TRH analogue raised CBF in the ischaemic region and suggested that its mechanism may be due to an increase of collateral flow 27 . JTP‐2942 increases acetylcholine release in the CNS 3 .…”

Section: Discussionmentioning

confidence: 99%

Delayed Administration Of Jtp‐2942, A Novel Thyrotropin‐Releasing Hormone Analogue, Improves Cerebral Blood Flow And Metabolism In Rat Postischaemic Brain

Katsumata

Katayama

Yonemori

et al. 2001

Clin Exp Pharma Physio

View full text Add to dashboard Cite

1. The aim of the present study was to examine the central nervous system action of JTP-2942, a novel thyrotropin-releasing hormone (TRH) analogue, from the point of view of cerebral blood flow (CBF) and metabolism in the postischaemic brain. 2. Left middle cerebral artery ischaemia was induced for 90 min followed by reperfusion. 3. Animals were separated into four groups: (i) low-dose (0.003 mg/kg) JTP-2942; (ii) high-dose (0.03 mg/kg) JTP-2942; (iii) cystidine diphosphate choline (500 mg/kg); and (iv) saline. The test drug or saline was administered intravenously 1 week after ischaemia. 4. Local CBF and local cerebral glucose utilization were measured autoradiographically, adjacent sections were stained with haematoxylin-eosin and infarction size was measured. 5. JTP-2942 ameliorated the reduction of local CBF and glucose utilization except in the ischaemic core. In particular, the higher dose (0.03 mg/kg) of JTP-2942 significantly increased local CBF and glucose utilization not only in peri-infarcted areas, but also in distal and contralateral areas. 6. These results suggest that JTP-2942 treatment may be beneficial for improving cerebral circulation and metabolism in the postischaemic brain.

show abstract

“…In a model of unilateral carotid ligature in the gerbil, GM1 (or AG 12) reduced by 52% the mortality at 48 h and reduced the size of the infarction [68], These results have been controlled in man. The role of scavengers trapping free radicals remains controversial [62,[69][70][71], New molecules have appeared in the literature, such as MCI 186 [72], Finally, the protective role of RX 77368. a thyrotropin-releasing hormone analog, through possible vascular action is mentioned [73]. The hcmorrheological or fibrinolytic targets have deliberately been left out of this review, although these vascular avenues of investigation merit great consideration.…”

Section: Other Pharmacologic Approachesmentioning

confidence: 99%

Mechanistic Basis for the Development of Anti-Ischemic Drugs

Allain¹,

Decombe²,

Saiag³

et al. 1991

Cerebrovasc Dis

View full text Add to dashboard Cite

The pharmacology of cerebral ischemia features 100 molecules and 20 potentially interesting mechanisms for preventing the tissue damage induced by anoxia-ischemia. The intricacy and complexity of the mechanisms involved probably account for the absence of definite evidence for effectiveness in man. The molecules which act on mechanisms qualifying as common denominators or triggering off cascade reactions, appear to be the best candidates. In this respect, the action of calcium, neurotransmitters, excitatory amino acids and pyrimidinergic or purinergic processes has to be given priority. Guidelines for the development of anti-ischemic molecules should be issued urgently, insisting on models, evaluation criteria, intervention timing and the parameters to be monitored (e.g. temperature, glycemia, choice of animal species).

show abstract

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

Cited by 13 publications

References 0 publications

Effects of thyrotropin-releasing hormone on regional cerebral blood flow in man

Effects of thyrotropin-releasing hormone on regional cerebral blood flow in man

Delayed Administration Of Jtp‐2942, A Novel Thyrotropin‐Releasing Hormone Analogue, Improves Cerebral Blood Flow And Metabolism In Rat Postischaemic Brain

Mechanistic Basis for the Development of Anti-Ischemic Drugs

Contact Info

Product

Resources

About