Development of AMPA receptor and GABA B receptor-sensitive spinal hyper-reflexia after spinal air embolism in rat: a systematic neurological, electrophysiological and qualitative histopathological study.
Decompression sickness results from formation of bubbles in the arterial and venous system, resulting in spinal disseminated neurodegenerative changes and may clinically be presented by motor dysfunction, spinal segmental stretch hyper-reflexia (i.e., spasticity) and muscle rigidity. In our current study, we describe a rat model of spinal air embolism characterized by the development of similar spinal disseminated neurodegenerative changes and functional deficit. In addition, the anti-spastic potency of systemic AMPA receptor antagonist (NGX424) or GABA B receptor agonist (baclofen) treatment was studied. To induce spinal air embolism, animals received an intra-aortic injection of air (50-200 μl/kg). After embolism, the development of spasticity was measured using computer-controlled ankle rotation. Animals receiving 150 or 200 μl of intra-aortic air injections displayed motor dysfunction with developed spastic (50-60% of animals) or flaccid (25-35% of animals) paraplegia at 5-7 days. MRI and spinal histopathological analysis showed disseminated spinal cord infarcts in the lower thoracic to sacral spinal segments. Treatment with NGX424 or baclofen provided a potent anti-spasticity effect (i.e., stretch hyper-reflexia inhibition). This model appears to provide a valuable experimental tool to study the pathophysiology of air embolism-induced spinal injury and permits the assessment of new treatment efficacy targeted to modulate neurological symptoms resulting from spinal air embolism.
Neuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92037, USA.
Osamu
O
Kakinohana
Miriam
M
Scadeng
Jose A
JA
Corleto
Juraj
J
Sevc
Nadezda
N
Lukacova
Martin
M
Marsala
D000818:Animals; D021721:Balloon Occlusion / Q000379:methods; D004618:Embolism, Air / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D010264:Paraplegia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D012021:Reflex, Abnormal / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
D018091:Receptors, AMPA; D018080:Receptors, GABA-B