PMID- 11794592
DA - 20020116
DCOM- 20020131
IS - 0022-3085
VI - 96
IP - 1
DP - 2002 Jan
TI - Hippocampal injury and neurobehavioral deficits following hyperglycemic cerebral ischemia: effect of theophylline and ZM 241385.
PG - 117-26 AB - OBJECT: The effects of the adenosine receptor antagonists theophylline (for A1 and A2) and ZM 241385 (for A2A) on hippocampal injury and Morris water maze (MWM) performance in rats were investigated following normoglycemic and hyperglycemic cerebral ischemia (induced by four vessel occlusion for 10 minutes). METHODS: Theophylline (36 mg/kg), ZM 241385 (1 mg/kg), or an equivalent volume of saline was administered to rats intraperitoneally 30 minutes before ischemia was induced. Moderate hyperglycemia was achieved by intraperitoneal administration of D-glucose (3 g/kg, 15 minutes before induction of ischemia). Morris water maze trials were performed on the 6th. 7th, and 8th days after ischemic insult. After the conclusion of the performance tests, the rat brains were cut into 8-microm sections, stained with cresyl violet and acid fuchsin, and evaluated in a blinded fashion to determine the extent of injury. Theophylline worsened injury in the hippocampus following normoglycemic and hyperglycemic ischemia. Moreover, theophylline significantly (p < 0.05, six animals) worsened latency and learning index (LI) scores during the MWM trials in both normoglycemic and hyperglycemic animals. On the other hand, ZM 241385 had no effect on either ischemic injury or MWM performance in normoglycemic animals. In the animals in the hyperglycemic ischemia group, however, ZM 241385 significantly (p < 0.05, five animals) reduced injury in the CA1 (94.6 +/- 1.7% compared with 79.2 +/- 10.9%), CA3 (26 +/- 12.5% compared with 11.2 +/- 4.3%), and hilum (22.4 +/- 8.1% compared with 11 +/- 5.5%) regions. In addition, ZM 241385 significantly improved latency (52 +/- 29.7 seconds compared with 24.8 +/- 11.2 seconds, p < 0.05) and LI scores (203.2 +/- 33.3 compared with 152.1 +/- 31.8, p < 0.05) in the MWM trials. A statistically significant correlation was also found between hippocampal injury (CA1, CA3, and hilum) and MWM performance. CONCLUSIONS: The results of this study provide further evidence for a neuromodulatory role of adenosine during normoglycemic and hyperglycemic ischemia.
AD - Department of Neurological Surgery, University of Washington, Seattle
98104, USA.
FAU - Higashi, Hisato
AU - Higashi H
FAU - Meno, Joseph R
AU - Meno JR
FAU - Marwaha, Amitoj S
AU - Marwaha AS
FAU - Winn, H Richard
AU - Winn HR
LA - eng
ID - NS-21076/NS/NINDS
PT - Journal Article
CY - United States
TA - J Neurosurg
JID - 0253357
RN - 0 (Blood Glucose)
RN - 0 (Receptors, Purinergic P1)
RN - 0 (Triazines)
RN - 0 (Triazoles)
RN - 0 (ZM 241385)
RN - 58-55-9 (Theophylline)
RN - 58-61-7 (Adenosine)
SB - AIM
SB - IM
MH - Adenosine/physiology
MH - Animal
MH - Blood Glucose/*metabolism
MH - Cell Death/drug effects
MH - Cerebral Infarction/*pathology
MH - Escape Reaction/*drug effects/physiology
MH - Hippocampus/*drug effects/pathology
MH - Injections, Intraperitoneal
MH - Male
MH - Maze Learning/*drug effects/physiology
MH - Neurons/drug effects/pathology
MH - Rats
MH - Rats, Wistar
MH - Receptors, Purinergic P1/*antagonists & inhibitors/physiology
MH - Support, U.S. Gov't, P.H.S.
MH - Theophylline/*pharmacology
MH - Triazines/*pharmacology
MH - Triazoles/*pharmacology
EDAT- 2002/01/17 10:00
MHDA- 2002/02/01 10:01
PST - ppublish
SO - J Neurosurg 2002 Jan;96(1):117-26.