Protective efficacy of a hypothermic pharmacological agent in gerbil forebrain ischemia.

Hall, Edward D.; Andrus, Paula K.; Pazara, K E

doi:10.1161/01.str.24.5.711

Cited by 27 publications

(4 citation statements)

References 32 publications

(1 reference statement)

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“…Histological outcomc was assessed at 4 and 21 days after ischemia. Uccause hyporhermia from physical or pharmacological intervention is an effective cerebral tieuroprotectant (Busto ct al., 1987;Welsh et al, 1990: Dietrich et al, 1993Hall et al, 1993;Colbourne and Corbett, 1994), we also assessed the role of hypothermia in tiagabine-mediated protection. These results have been presented previously in a preliminary form (Inglcfield et al, 1994).…”

mentioning

confidence: 99%

Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus

Inglefield¹,

Perry²,

Schwartz³

1995

Hippocampus

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The neuroprotective effects of enhancing neuronal inhibition with a gamma-aminobutyric acid (GABA) uptake inhibitor were studied in gerbil hippocampus following transient ischemia. We used in vivo microdialysis to determine a suitable dosing regimen for tiagabine (NNC328) to elevate extracellular levels of GABA within the hippocampus. In anesthetized (normothermic) gerbils, tiagabine (45 mg/kg, i.p.) selectively elevated extracellular GABA levels 450% in area CA1 of the hippocampus. In gerbils subjected to cerebral ischemia via 5-min bilateral carotid occlusion, extracellular GABA levels increased 13-fold in area CA 1 returning to baseline within 30-45 min. When tiagabine was injected 10 min following onset of reperfusion, GABA levels remained elevated (200-470%) for 90 min. In addition, tiagabine significantly reduced the ischemic-induced elevation of glutamate levels in area CA1 during the postischemic period when GABA levels were elevated. There was no effect of postischemic tiagabine on aspartate or six other amino acids. Using the same dosing regimen, we evaluated the degree of neuroprotection in the hippocampus of gerbils 4 and 21 days after ischemia. Tiagabine decreased body temperature a maximum of 2.7 degrees C beginning 30 min into reperfusion and lasting 90 min. In untreated gerbils sacrificed 4 and 21 days after ischemia, there was severe necrosis (99%) of the pyramidal cell layer in area CA1. Whereas tiagabine significantly protected the CA1 pyramidal cell layer in ischemic gerbils at 4 days (overt necrosis confined to about 17% of area CA1), the protection diminished significantly 21 days postischemia. When normothermia was maintained both during and after ischemia in a separate group of tiagabine-treated animals, approximately 77% of the CA1 pyramidal cell layer was necrotic at 4 days. Based on these findings, we suggest that 1) tiagabine slows the development of hippocampal degeneration following ischemia, and 2) that mild, postischemic hypothermia is responsible, in large part, for the neuroprotective actions of this drug. We conclude that the histological outcome after administration of cerebral neuroprotectants should be assessed following long-term survival.

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mentioning

confidence: 99%

Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus

Inglefield¹,

Perry²,

Schwartz³

1995

Hippocampus

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“…However, other more selective central nervous system cholinergic agonists can produce hypothermia with reduced peripheral effects. 3 A recent article 4 has shown that such drugs, when administered before induction of temporary forebrain ischemia and during reperfusion in a gerbil model, produce reduction in the amount of neuronal loss by their hypothermic effect. The temperature reduction of approximately 2°C produced in these experiments would be expected to have profound cerebral protective effects.…”

Section: Pharmacologically Induced Hypothermia For Cerebral Protectiomentioning

confidence: 99%

“…These are, of course, measurements of spatial peak-temporal average (SPTA) made in water, and the maximum value is reduced to 240 mW/cm 2 by the application of the Food and Drug Administration's formula originally used for estimating in situ intensity for fetal insonation 4 and to 51 mW/cm 2 by using the unit of estimated intracranial intensity (EII) proposed by me as being more realistic for TCD applications. .…”

Section: Effect Of Emitted Power On Waveform Intensity In Transcraniamentioning

confidence: 99%

Pharmacologically induced hypothermia for cerebral protection in humans.

Menon¹,

Young²

1994

Stroke

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“…Several candidates targeting distinct signaling pathways have been tested for PIH including a neurotensin receptor agonist HPI201/ABS201 in stroke and TBI models [3, 4], a cannabinoid receptor agonist WIN55, 212-2 in a ventricular defibrillation CA model [5], the A1 adenosine receptor agonist 8-SPT in an asphyxial-CA model [6], the muscarinic cholinergic partial agonist U-80816E in the gerbil brief bilateral carotid occlusion ischemia model [7], a dopaminergic agonist Talipexole in stroke model [8], a serotonergic agonist S14671 in a stroke model [9] and the transient receptor potential cation channel vanilloid type 1 (TRPV1) agonist dihydrocapsaicin (DHC) in a stroke model [10]. …”

Section: Introductionmentioning

confidence: 99%

Dihydrocapsaicin-induced hypothermia after asphyxiai cardiac arrest in rats

Young

Jia

2016

2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

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Cardiac arrest (CA) is one of the leading causes of mortality and morbidity in the world. Fast, reversible and controllable pharmaceutical-induced hypothermia (PIH) is strongly desired to treat ischemia-reperfusion brain injury. Dihydrocapsaicin (DHC), an agonist of transient receptor potential vanilloid type 1 cation channel (TRPV1), is an emerging candidate for PIH. Its capability to lower body temperature has been validated in both healthy and stroke animal models. However, DHC has shown cardiovascular effects and its safety and feasibility in a CA model has not been tested. Additionally, activated TRPV1 has multiple functions in addition to regulating body temperature and its effect on neurological recovery needs to be evaluated. In this study, we compared two methods of DHC administration, bolus injection and infusion via the femoral vein. We found that cardiovascular effects were only seen with a large dose DHC bolus injection. Then, we applied DHC-induced hypothermia in an asphyxial-CA rat model. We showed that DHC-treated rats were viable. Four-hour infusion of DHC at a rate of 0.75 mg/kg/h after CA maintained a body temperature of about 34 °C for at least 8 hours. DHC-treated rats had higher electrical activity during the first 4 hours after CA and had better neurological recovery during the 3 days after CA compared with normothermia rats. Additional pathway investigation of DHC administration following CA will further uncover the benefits of DHC-induced hypothermia.

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Protective efficacy of a hypothermic pharmacological agent in gerbil forebrain ischemia.

Abstract: Background and Purpose: The novel muscarinic cholinergic partial agonist U-80816E was tested in the gerbil brief bilateral carotid occlusion ischemia model based on the rationale that the compound's

Cited by 27 publications

References 32 publications

Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus

Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus

Pharmacologically induced hypothermia for cerebral protection in humans.

Dihydrocapsaicin-induced hypothermia after asphyxiai cardiac arrest in rats

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