title: Blockade of acute hypertensive response does not prevent changes in behavior or in CSF acetylcholine (ACH) content following traumatic brain injury (TBI).
abstract: There is evidence that the blood-brain barrier (BBB) is breached following traumatic brain injury (TBI), allowing the unregulated entry of circulating neuroactive substances into the central nervous system. As the traumatic episode is typically associated with an acute hypertensive event, which in itself may alter BBB status, the effects of the blockade of TBI-associated hypertension on injury-associated behavioral and cerebrospinal fluid (CSF) neurochemical changes were assessed in rats. Animals were injected with either saline or hexamethonium 15 min prior to a moderate fluid percussion injury while under light methoxyflurane anesthesia. This dose of hexamethonium was demonstrated to block the hypertensive response to TBI. Pretreatment with hexamethonium prevented neither acute nor more enduring behavioral deficits observed after TBI. Hexamethonium did not prevent TBI-associated increases in CSF acetylcholine (ACh) content in separate group of rats sampled 12 min following TBI. Furthermore, histological inspection indicated that hexamethonium did not prevent TBI-induced disruption of the BBB, as assessed by intravascular horseradish peroxidase (HRP). Thus, blockade of the hypertensive response to TBI does not afford behavioral protection nor does it prevent changes in the BBB or CSF ACh content following TBI. TBI is in itself sufficient to modify behavior, neurochemistry and BBB function in the absence of hypertension.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
authors.forename: E K
authors.initials: EK
authors.lastname: Enters
authors.forename: J R
authors.initials: JR
authors.lastname: Pascua
authors.forename: K P
authors.initials: KP
authors.lastname: McDowell
authors.forename: M Z
authors.initials: MZ
authors.lastname: Kapasi
authors.forename: J T
authors.initials: JT
authors.lastname: Povlishock
authors.forename: S E
authors.initials: SE
authors.lastname: Robinson
mesh_terms: D000109:Acetylcholine / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D000818:Animals; D001370:Axonal Transport; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D004924:Escape Reaction / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology*; D006735:Horseradish Peroxidase; D006973:Hypertension / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D006584:Hexamethonium Compounds; D018738:Hexamethonium; D006735:Horseradish Peroxidase; D000109:Acetylcholine