Loss of long-term potentiation in the hippocampus after experimental subarachnoid hemorrhage in rats.
Survivors of aneurysmal subarachnoid hemorrhage (SAH) often suffer from cognitive impairment such as memory loss. However, the underlying mechanisms of these impairments are not known. Long-term potentiation (LTP) of synapses in the hippocampus is generally regarded as a molecular substrate of memory. The purpose of this study was to examine the effect of SAH on LTP in the hippocampal Schaffer collateral (CA3-CA1) pathway in a rat model of SAH. We found SAH caused significant vasospasm of the middle cerebral artery (MCA) compared to saline injected or sham controls (P<0.001). Basic neurotransmission quantified as excitatory post synaptic and spike response from animals with SAH were significantly decreased as compared to naive controls (P<0.05). However, sham operated and saline injected controls showed similar amplitude as naive controls. This suggests that reduction in basic neurotransmission is due to blood in the subarachnoid space. Similarly, analysis of LTP demonstrated that naive, sham and saline controls have a 92+/-16%, 69+/-27% and 71+/-14% increase over the baseline in the average spike amplitude following high frequency stimulation (HFS), respectively. This indicates the presence of LTP (P<0.05). In contrast, the spike amplitude in animals of SAH returned to baseline level within 60 min post HFS indicating the absence of LTP. We conclude that SAH caused vasospasm of the MCA that was associated with disrupted basic neurotransmission and plasticity at CA3-CA1 synapses. These changes might be accountable for the memory loss in humans with SAH.
Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada.
A
A
Tariq
J
J
Ai
G
G
Chen
M
M
Sabri
H
H
Jeon
X
X
Shang
R L
RL
Macdonald
D000200:Action Potentials; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D056654:CA3 Region, Hippocampal / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D020768:Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*