Glucocorticoids aggravate retrograde memory deficiency associated with traumatic brain injury in rats.
Administration of glucocorticoid to patients with head injury has previously been demonstrated to impair memory. We hypothesize that glucocorticoids promote post-traumatic hippocampal apoptosis, resulting in retrograde memory deficiency associated with traumatic brain injury (TBI). In the present study, we tested this hypothesis by measuring spatial memory deficiency in rats subjected to fluid percussion injury (FPI) and receiving dexamethasone (DXM at 0.5-10 mg/kg) or methylprednisolone (MP at 5-30 mg/kg); we also examined neuronal apoptosis in hippocampus. Adult male Wistar rats were trained for the acquisition of spatial memory, then subjected to FPI and tested for spatial reference memory on post-injury days 7 and 14 using the Morris Water Maze. Brain tissue from injured rats was examined 24 h to 2 weeks after injury. The percent time in the goal quadrant, which measures spatial reference memory, was significantly lower in injured rats receiving either high-dose DXM or MP than in control groups. TUNEL-positive cells in hippocampus were first detected 24 h post-injury, plateauing at 48h. The number of TUNEL-positive cells was significantly higher in injured rats treated with either DXM or MP. The data suggest that glucocorticoid therapy for TBI may increase neuronal apoptosis in hippocampus and, as a result, aggravate retrograde memory deficits induced by TBI.
Chen
Xin
X
Department of Neurosurgery, Tianjin Neurological Institute, General Hospital, Tianjin Medical University, Tianjin, China.
Zhang
Ke-Li
KL
Yang
Shu-Yuan
SY
Dong
Jing-Fei
JF
Zhang
Jian-Ning
JN
D000648:Amnesia, Retrograde / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects
D005938:Glucocorticoids; D003907:Dexamethasone; D008775:Methylprednisolone