Combined pretrauma scopolamine and phencyclidine attenuate posttraumatic increased sensitivity to delayed secondary ischemia.
Fasted Wistar rats were given a mild level of traumatic brain injury (TBI) and then subjected to 6 min of transient forebrain ischemia 24 h posttrauma. One group was given simultaneous 1 mg/kg scopolamine and 4 mg/kg phencyclidine intraperitoneally (IP) 15 min before trauma and another group an equal volume of plasmalyte A solution. After 7 days of postinjury survival, placebo-treated rats demonstrated increased posttraumatic vulnerability to secondary ischemic CA1 neuronal death even 24 h after trauma. This finding confirmed that increased posttraumatic ischemic vulnerability persists for at least 24 h even following mild trauma. Combined muscarinic receptor and N-methyl-D-aspartate (NMDA) receptor coupled ion channel blockade given and present during the mild TBI statistically attenuated this enhanced secondary ischemic CA1 neuronal death and thus posttraumatic increased ischemic vulnerability. Placebo-treated rats had 335.3 +/- 93.6 CA1 neurons/10(6) microns 2 and drug-treated rats had 844.8 +/- 184.9 CA1 neurons/10(6) microns 2. This result suggests that muscarinic and/or NMDA receptor-mediated events confined to TBI and the early posttraumatic period are in part responsible for the phenomenon of increased posttraumatic ischemic vulnerability.
Jenkins
L W
LW
Department of Anesthesiology, Medical College of Virginia, Richmond.
Lyeth
B G
BG
Lewelt
W
W
Moszynski
K
K
Dewitt
D S
DS
Balster
R L
RL
Miller
L P
LP
Clifton
G L
GL
Young
H F
HF
Hayes
R L
RL
D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004338:Drug Combinations; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010622:Phencyclidine / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine / Q000627:therapeutic use*
D004338:Drug Combinations; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D012601:Scopolamine; D010622:Phencyclidine