cx717 and Spinal-Cord-Injuries

Topics: Animals; Cervical Cord; Cervical Vertebrae; Diaphragm; Electromyography; Female; Isoxazoles; Male; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Spinal Cord Injuries

Activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors increases phrenic motor output. Ampakines are a class of drugs that are positive allosteric modulators of AMPA receptors. We hypothesized that 1) ampakines can stimulate phrenic activity after incomplete cervical spinal cord injury (SCI), and 2) pairing ampakines with brief hypoxia could enable sustained facilitation of phrenic bursting. Phrenic activity was recorded ipsilateral (IL) and contralateral (CL) to C2 spinal cord hemisection (C2Hx) in anesthetized adult rats. Two weeks after C2Hx, ampakine CX717 (15 mg/kg, i.v.) increased IL (61 ± 46% baseline, BL) and CL burst amplitude (47 ± 26%BL) in 8 of 8 rats. After 90 min, IL and CL bursting remained above baseline (BL) in 7 of 8 rats. Pairing ampakine with a single bout of acute hypoxia (5-min, arterial partial pressure of O

Topics: Animals; Cervical Vertebrae; Diaphragm; Isoxazoles; Male; Motor Neurons; Organ Culture Techniques; Phrenic Nerve; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries