CGS-19755 is neuroprotective during repetitive ischemia: This effect is significantly enhanced when combined with hypothermia

Shuaib, Ashfaq; Ijaz, Sadiq; Mazagri, Rida; Senthilsevlvan, A.

doi:10.1016/0306-4522(93)90137-5

Cited by 33 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…45 The efficacy of CGS-19755, a competitive NMDA antagonist, was significantly enhanced when combined with mild, intraischemic hypothermia (34°C) in gerbils surviving up to 1 month after forebrain ischemia. 46,47 In contrast, protection with postischemic hypothermia alone was not evident after 1 month. 48 Similarly, Coimbra et al 49 found that treatment with postischemic hypothermia alone delayed neuronal damage after global ischemia in rats, but combined treatment with hypothermia and dipyrone, an antiinflammatory drug, diminished neuronal damage by Ͼ50% at both 7 days and 2 months of recovery.…”

Section: Combination Of Hypothermia and Pharmacotherapymentioning

confidence: 83%

Combination Drug Therapy and Mild Hypothermia

Schmid-Elsaesser

Hungerhuber

Zausinger

et al. 1999

Stroke

View full text Add to dashboard Cite

Background and Purpose-Hypothermia has been suggested to be the most potent therapeutic approach to reduce experimental ischemic brain injury identified to date, and mild hypothermia is increasingly used for neuroprotection during neurovascular surgery. We have recently demonstrated that combined administration of tirilazad mesylate and magnesium provides for an overall enhanced neuroprotective effect. The present study was designed to determine whether the efficacy of mild hypothermia (33°C) can be increased by combination pharmacotherapy with tirilazad and magnesium (MgCl 2 ). Methods-Forty Sprague-Dawley rats were subjected to transient, middle cerebral artery occlusion and were randomly assigned to 1 of 4 treatment arms (nϭ10 each): (1) normothermiaϩvehicle, (2) normothermiaϩtirilazadϩMgCl 2 , (3) hypothermiaϩvehicle, or (4) hypothermiaϩtirilazadϩMgCl 2 . Cortical blood flow was monitored by a bilateral laser-Doppler flowmeter, and the electroencephalogram was continuously recorded. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed after 7 days. Results-TirilazadϩMgCl 2 , hypothermia, and hypothermiaϩtirilazadϩMgCl 2 reduced total infarct volume by 56%, 63%, and 77%, respectively, relative to controls. In animals treated with both hypothermia and combination pharmacotherapy, cortical infarction was almost completely abolished (Ϫ99%), and infarct volume in the basal ganglia was significantly reduced by 55%. In addition, this treatment provided for the best electrophysiological recovery and functional outcome. Conclusions-The neuroprotective efficacy of hypothermia can be increased by pharmacological antagonism of excitatory amino acids and free radicals by using clinically available drugs. This treatment strategy could be of great benefit when applied during temporary artery occlusion in cerebrovascular surgery. (Stroke. 1999;30:1891-1899.)

show abstract

Section: Combination Of Hypothermia and Pharmacotherapymentioning

confidence: 83%

Combination Drug Therapy and Mild Hypothermia

Schmid-Elsaesser

Hungerhuber

Zausinger

et al. 1999

Stroke

View full text Add to dashboard Cite

show abstract

“…The rectal temperature of each rat was kept at 37°C throughout the surgery procedure with a feedback controlled heating system. In hypothermia groups, temperature was instituted by spraying 100% alcohol on the body of the rat while a fan circulated room air around the animal, detailed previously [14,15]. The rectal temperature was kept at 34–35°C during the hypothermia period.…”

Section: Methodsmentioning

confidence: 99%

“…A mild degree of hypothermia was chosen since it protects neurons from damage in both focal and global ischemic injury [3,5,9,10,14]. We also found that the mild hypothermia possessed an additive effect to the protective actions of anti-glutamate agent in a global ischemic injury model [15]. Furthermore, study has shown a high correlation between brain and rectal temperatures in focal ischemic brain injury model, with brain temperature being higher than rectal temperature by 0.2 to 0.7°C [9].…”

Section: Methodsmentioning

confidence: 99%

“…In a rat model of ischemia induced by occlusion of the middle cerebral artery (MCA) with a suture, minocycline is also an effective neuroprotective agent [21]. Mild hypothermia induced before and after ischemic brain injury reduces the structural, metabolic and behavioral changes due to ischemia [4,14,15]. In global ischemic injury model of repetitive forebrain ischemia, we have demonstrated that mild hypothermia protects neurons from damage [14].…”

Section: Introductionmentioning

confidence: 99%

“…In global ischemic injury model of repetitive forebrain ischemia, we have demonstrated that mild hypothermia protects neurons from damage [14]. We and other group have also shown that the protective effect of mild hypothermia can be enhanced by combination with other neuroprotective agents in global ischemic injury model [3,5,15]. Mild hypothermia in combination with anti-inflammatory treatment provides long-lasting neuroprotection of CA1 hippocampus following transient global ischemia [3,5].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations