Abstract
Hippocampal levels of fatty acids extracted from phosphatidylinositol 4,5-bisphosphate (PIP2), free fatty acids (FFA), and lactate were measured after central fluid percussion traumatic brain injury (TBI) in rats. At 5 min after injury, there was a decrease in fatty acids extracted from PIP2 suggesting a decrease in PIP2. At the same time point, total FFA increased in saline-treated TBI rats. Levels of arachidonic acid were significantly decreased in PIP2, while at the same time arachidonic and stearic acids increased in FFA in saline-treated TBI rats. No significant alterations in PIP2-derived fatty acids or FFA were observed at 20 min after TBI. Hippocampal concentrations of lactate were significantly elevated at 5 and 20 min after injury in saline-treated rats. In general, these alterations were blunted by preinjury administration of the muscarinic antagonist, scopolamine. These results suggest that the PIP2 signal transduction pathway is activated in the hippocampus at the onset of central fluid percussion TBI and that the enhanced phospholipase C-catalyzed phosphodiestric breakdown of PIP2 is a major mechanism of liberation of FFA in these sites immediately after such injury. The blunting of PIP2 and FFA alterations in animals treated with scopolamine suggests that activation of muscarinic receptors significantly contributes to the phospholipase C (PLC) signal transduction pathophysiology in TBI. The attenuation of lactate accumulation in scopolamine-treated rats suggests that TBI-induced muscarinic receptor activation also contributies to increased glycolytic metabolism and/or ionic imbalances.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 63-70 |
| Number of pages | 8 |
| Journal | Brain Research |
| Volume | 742 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Dec 2 1996 |
| Externally published | Yes |
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Keywords
- arachidonic acid
- diacylglycerol
- fluid percussion
- free fatty acid
- muscarinic
- phosphatidylinositol bisphosphate
- rat
- scopolamine
- traumatic brain injury
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Effects of muscarinic receptor antagonism on the phosphatidylinositol bisphosphate signal transduction pathway after experimental brain injury. / Lyeth, Bruce G; Gong, Qin Zhi; Dhillon, H. S.; Prasad, M. Renuka.
In: Brain Research, Vol. 742, No. 1-2, 02.12.1996, p. 63-70.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of muscarinic receptor antagonism on the phosphatidylinositol bisphosphate signal transduction pathway after experimental brain injury
AU - Lyeth, Bruce G
AU - Gong, Qin Zhi
AU - Dhillon, H. S.
AU - Prasad, M. Renuka
PY - 1996/12/2
Y1 - 1996/12/2
N2 - Hippocampal levels of fatty acids extracted from phosphatidylinositol 4,5-bisphosphate (PIP2), free fatty acids (FFA), and lactate were measured after central fluid percussion traumatic brain injury (TBI) in rats. At 5 min after injury, there was a decrease in fatty acids extracted from PIP2 suggesting a decrease in PIP2. At the same time point, total FFA increased in saline-treated TBI rats. Levels of arachidonic acid were significantly decreased in PIP2, while at the same time arachidonic and stearic acids increased in FFA in saline-treated TBI rats. No significant alterations in PIP2-derived fatty acids or FFA were observed at 20 min after TBI. Hippocampal concentrations of lactate were significantly elevated at 5 and 20 min after injury in saline-treated rats. In general, these alterations were blunted by preinjury administration of the muscarinic antagonist, scopolamine. These results suggest that the PIP2 signal transduction pathway is activated in the hippocampus at the onset of central fluid percussion TBI and that the enhanced phospholipase C-catalyzed phosphodiestric breakdown of PIP2 is a major mechanism of liberation of FFA in these sites immediately after such injury. The blunting of PIP2 and FFA alterations in animals treated with scopolamine suggests that activation of muscarinic receptors significantly contributes to the phospholipase C (PLC) signal transduction pathophysiology in TBI. The attenuation of lactate accumulation in scopolamine-treated rats suggests that TBI-induced muscarinic receptor activation also contributies to increased glycolytic metabolism and/or ionic imbalances.
AB - Hippocampal levels of fatty acids extracted from phosphatidylinositol 4,5-bisphosphate (PIP2), free fatty acids (FFA), and lactate were measured after central fluid percussion traumatic brain injury (TBI) in rats. At 5 min after injury, there was a decrease in fatty acids extracted from PIP2 suggesting a decrease in PIP2. At the same time point, total FFA increased in saline-treated TBI rats. Levels of arachidonic acid were significantly decreased in PIP2, while at the same time arachidonic and stearic acids increased in FFA in saline-treated TBI rats. No significant alterations in PIP2-derived fatty acids or FFA were observed at 20 min after TBI. Hippocampal concentrations of lactate were significantly elevated at 5 and 20 min after injury in saline-treated rats. In general, these alterations were blunted by preinjury administration of the muscarinic antagonist, scopolamine. These results suggest that the PIP2 signal transduction pathway is activated in the hippocampus at the onset of central fluid percussion TBI and that the enhanced phospholipase C-catalyzed phosphodiestric breakdown of PIP2 is a major mechanism of liberation of FFA in these sites immediately after such injury. The blunting of PIP2 and FFA alterations in animals treated with scopolamine suggests that activation of muscarinic receptors significantly contributes to the phospholipase C (PLC) signal transduction pathophysiology in TBI. The attenuation of lactate accumulation in scopolamine-treated rats suggests that TBI-induced muscarinic receptor activation also contributies to increased glycolytic metabolism and/or ionic imbalances.
KW - arachidonic acid
KW - diacylglycerol
KW - fluid percussion
KW - free fatty acid
KW - muscarinic
KW - phosphatidylinositol bisphosphate
KW - rat
KW - scopolamine
KW - traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=0030566694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030566694&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(96)01002-5
DO - 10.1016/S0006-8993(96)01002-5
M3 - Article
VL - 742
SP - 63
EP - 70
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -