Injury-induced alterations in CNS electrophysiology.
Mild to moderate cases of traumatic brain injury (TBI) are very common, but are not always associated with the overt pathophysiogical changes seen following severe trauma. While neuronal death has been considered to be a major factor, the pervasive memory, cognitive and motor function deficits suffered by many mild TBI patients do not always correlate with cell loss. Therefore, we assert that functional impairment may result from alterations in surviving neurons. Current research has begun to explore CNS synaptic circuits after traumatic injury. Here we review significant findings made using in vivo and in vitro models of TBI that provide mechanistic insight into injury-induced alterations in synaptic electrophysiology. In the hippocampus, research now suggests that TBI regionally alters the delicate balance between excitatory and inhibitory neurotransmission in surviving neurons, disrupting the normal functioning of synaptic circuits. In another approach, a simplified model of neuronal stretch injury in vitro, has been used to directly explore how injury impacts the physiology and cell biology of neurons in the absence of alterations in blood flow, blood brain barrier integrity, or oxygenation associated with in vivo models of brain injury. This chapter discusses how these two models alter excitatory and inhibitory synaptic transmission at the receptor, cellular and circuit levels and how these alterations contribute to cognitive impairment and a reduction in seizure threshold associated with human concussive brain injury.
Cohen
Akiva S
AS
Department of Pediatrics, University of Pennsylvania, School of Medicine and Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Cohena@email.chop.edu
Pfister
Bryan J
BJ
Schwarzbach
Elizabeth
E
Grady
M Sean
MS
Goforth
Paulette B
PB
Satin
Leslie S
LS
D000818:Animals; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000503:physiopathology; D002490:Central Nervous System / Q000293:injuries* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology; D020196:Trauma, Nervous System / Q000503:physiopathology*
D017981:Receptors, Neurotransmitter