Blockade of histamine H2 receptors attenuate blood-brain barrier permeability, cerebral blood flow disturbances, edema formation and cell reactions following hyperthermic brain injury in the rat.
Role of histamine H2 receptors in blood-brain barrier (BBB) disturbances, cerebral blood flow (CBF), brain edema formation, and cell injury caused by heat stress in a rat model was examined using the pharmacological approach. Blockade of histamine H2 receptors by cimetidine or ranitidine significantly attenuated the BBB permeability to Evans blue albumin and [131]I-sodium extravasation, brain edema formation and cell injury following 4 h heat stress in rats at 38 degrees C. These drug treatments also restored the CBF to near normal values. These beneficial effects in heat stress were most marked in rats treated with ranitidine compared to cimetidine given in identical dosage. Our observations suggest that blockade of histamine H2 receptor is beneficial in hyperthermic brain injury and indicates that histamine is involved in the pathophysiology of heat stress induced brain dysfunction. Our study strongly suggests further need to develop more specific and sensitive histaminergic H2 receptor blockers for the treatment of neurological ailments.
Patnaik
R
R
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Mohanty
S
S
Sharma
H S
HS
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply*; D001929:Brain Edema / Q000503:physiopathology*; D001930:Brain Injuries / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology*; D018882:Heat Stress Disorders / Q000503:physiopathology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects
D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; D002927:Cimetidine; D011899:Ranitidine