Estimation of the hypothermic component in neuroprotection provided by cannabinoids following cerebral ischemia.

Peter K Bonfils; Jakob Reith; Henrik Hasseldam; Flemming Fryd Johansen

doi:10.1016/j.neuint.2006.03.015

Estimation of the hypothermic component in neuroprotection provided by cannabinoids following cerebral ischemia.

Peter K Bonfils, Jakob Reith, Henrik Hasseldam, Flemming Fryd Johansen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

28 Citationer (Scopus)

Abstract

Udgivelsesdato: 2006-Oct

Originalsprog	Engelsk
Tidsskrift	Neurochemistry International
Vol/bind	49
Udgave nummer	5
Sider (fra-til)	508-18
Antal sider	10
ISSN	0197-0186
DOI	https://doi.org/10.1016/j.neuint.2006.03.015
Status	Udgivet - 2006
Udgivet eksternt	Ja

Bibliografisk note

Keywords: Animals; Benzoxazines; Brain Ischemia; Enzyme-Linked Immunosorbent Assay; Hypothermia; Male; Morpholines; Naphthalenes; Neuroprotective Agents; Rats; Rats, Wistar

Adgang til dokumentet

10.1016/j.neuint.2006.03.015

Citationsformater

@article{ea5de9d05d6b11dd8d9f000ea68e967b,

title = "Estimation of the hypothermic component in neuroprotection provided by cannabinoids following cerebral ischemia.",

abstract = "Cannabinoids have neuroprotective potentials, and the expression of endocannabinoids as well as cannabinoid receptors is induced after cerebral ischemia. They also induce hypothermia by lowering the hypothalamic set point. We have estimated the significance of such hypothermia in ischemic neuroprotection following systemic administration of WIN 55,212-2, a synthetic cannabinoid receptor agonist. Results showed that WIN 55,212-2 significantly reduced infarct volumes of rats subjected to focal cerebral ischemia (middle cerebral artery occlusion) and significantly decreased ischemic CA1 damage in rats subjected to global cerebral ischemia (two-vessel occlusion). A significant (approximately 50%) part of this neuroprotection was provided by WIN 55,212-2 induced hypothermia (33.7+/-1.1 degrees C/34.9+/-1.6 degrees C), because prevention of hypothermia by maintaining body core temperatures between 37.0 and 38.0 degrees C dissolved the neuroprotective effect into a hypothermic component and an unidentified component. Finally, the ability of WIN 55,212-2 to reduce levels of the proinflammatory cytokine IFNgamma in the infarcted hemisphere of rats subjected to focal cerebral ischemia required hypothermia. For the cannabinoid WIN 55,212-2, we have isolated and directly demonstrated that hypothermia is only part of, although significant, cannabinoid mediated neuroprotection in both global and focal cerebral ischemia. We conclude that cannabinoids are reliable candidates for drug-induced hypothermia and neuroprotection. These neuroprotective effects of cannabinoids could provide the basis for potential therapeutic uses of cannabinoids and/or endocannabinoids in stroke.",

author = "Bonfils, {Peter K} and Jakob Reith and Henrik Hasseldam and Johansen, {Flemming Fryd}",

note = "Keywords: Animals; Benzoxazines; Brain Ischemia; Enzyme-Linked Immunosorbent Assay; Hypothermia; Male; Morpholines; Naphthalenes; Neuroprotective Agents; Rats; Rats, Wistar",

year = "2006",

doi = "10.1016/j.neuint.2006.03.015",

language = "English",

volume = "49",

pages = "508--18",

journal = "Neurochemistry International",

issn = "0197-0186",

publisher = "Elsevier",

number = "5",

}

TY - JOUR

T1 - Estimation of the hypothermic component in neuroprotection provided by cannabinoids following cerebral ischemia.

AU - Bonfils, Peter K

AU - Reith, Jakob

AU - Hasseldam, Henrik

AU - Johansen, Flemming Fryd

N1 - Keywords: Animals; Benzoxazines; Brain Ischemia; Enzyme-Linked Immunosorbent Assay; Hypothermia; Male; Morpholines; Naphthalenes; Neuroprotective Agents; Rats; Rats, Wistar

PY - 2006

Y1 - 2006

N2 - Cannabinoids have neuroprotective potentials, and the expression of endocannabinoids as well as cannabinoid receptors is induced after cerebral ischemia. They also induce hypothermia by lowering the hypothalamic set point. We have estimated the significance of such hypothermia in ischemic neuroprotection following systemic administration of WIN 55,212-2, a synthetic cannabinoid receptor agonist. Results showed that WIN 55,212-2 significantly reduced infarct volumes of rats subjected to focal cerebral ischemia (middle cerebral artery occlusion) and significantly decreased ischemic CA1 damage in rats subjected to global cerebral ischemia (two-vessel occlusion). A significant (approximately 50%) part of this neuroprotection was provided by WIN 55,212-2 induced hypothermia (33.7+/-1.1 degrees C/34.9+/-1.6 degrees C), because prevention of hypothermia by maintaining body core temperatures between 37.0 and 38.0 degrees C dissolved the neuroprotective effect into a hypothermic component and an unidentified component. Finally, the ability of WIN 55,212-2 to reduce levels of the proinflammatory cytokine IFNgamma in the infarcted hemisphere of rats subjected to focal cerebral ischemia required hypothermia. For the cannabinoid WIN 55,212-2, we have isolated and directly demonstrated that hypothermia is only part of, although significant, cannabinoid mediated neuroprotection in both global and focal cerebral ischemia. We conclude that cannabinoids are reliable candidates for drug-induced hypothermia and neuroprotection. These neuroprotective effects of cannabinoids could provide the basis for potential therapeutic uses of cannabinoids and/or endocannabinoids in stroke.

AB - Cannabinoids have neuroprotective potentials, and the expression of endocannabinoids as well as cannabinoid receptors is induced after cerebral ischemia. They also induce hypothermia by lowering the hypothalamic set point. We have estimated the significance of such hypothermia in ischemic neuroprotection following systemic administration of WIN 55,212-2, a synthetic cannabinoid receptor agonist. Results showed that WIN 55,212-2 significantly reduced infarct volumes of rats subjected to focal cerebral ischemia (middle cerebral artery occlusion) and significantly decreased ischemic CA1 damage in rats subjected to global cerebral ischemia (two-vessel occlusion). A significant (approximately 50%) part of this neuroprotection was provided by WIN 55,212-2 induced hypothermia (33.7+/-1.1 degrees C/34.9+/-1.6 degrees C), because prevention of hypothermia by maintaining body core temperatures between 37.0 and 38.0 degrees C dissolved the neuroprotective effect into a hypothermic component and an unidentified component. Finally, the ability of WIN 55,212-2 to reduce levels of the proinflammatory cytokine IFNgamma in the infarcted hemisphere of rats subjected to focal cerebral ischemia required hypothermia. For the cannabinoid WIN 55,212-2, we have isolated and directly demonstrated that hypothermia is only part of, although significant, cannabinoid mediated neuroprotection in both global and focal cerebral ischemia. We conclude that cannabinoids are reliable candidates for drug-induced hypothermia and neuroprotection. These neuroprotective effects of cannabinoids could provide the basis for potential therapeutic uses of cannabinoids and/or endocannabinoids in stroke.

U2 - 10.1016/j.neuint.2006.03.015

DO - 10.1016/j.neuint.2006.03.015

M3 - Journal article

C2 - 16730099

SN - 0197-0186

VL - 49

SP - 508

EP - 518

JO - Neurochemistry International

JF - Neurochemistry International

IS - 5

ER -