title: Neurochemical excitation of thoracic propriospinal neurons improves hindlimb stepping in adult rats with spinal cord lesions.
abstract: Using an in vitro neonatal rat brainstem-spinal cord preparation, we previously showed that cervicothoracic propriospinal neurons contribute to descending transmission of the bulbospinal locomotor command signal, and neurochemical excitation of these neurons facilitates signal propagation. The present study examined the relevance of these observations to adult rats in vivo. The first aim was to determine the extent to which rats are able to spontaneously recover hindlimb locomotor function in the presence of staggered contralateral hemisections (left T2-4 and right T9-11) designed to abolish all long direct bulbospinal projections. The second aim was to determine whether neurochemical excitation of thoracic propriospinal neurons in such animals facilitates hindlimb stepping. In the absence of intrathecal drug injection, all animals (n=24) displayed some degree of hindlimb recovery ranging from weak ankle movements to brief periods of unsupported hindlimb stepping on the treadmill. The effect of boluses of neurochemicals delivered via an intrathecal catheter (tip placed midway between the rostral and caudal thoracic hemisections) was examined at post-lesion weeks 3, 6 and 9. Quipazine was particularly effective facilitating hindlimb stepping. Subsequent complete transection above the rostral (n=3) or caudal (n=2) hemisections at week 9 had no consistent effect on drug-free locomotor performance, but the facilitatory effect of drug injection decreased in 4/5 animals. Two animals underwent complete transection at T3 as the first and only surgery and implantation of two intrathecal catheters targeted to the mid-thoracic and lumbar regions, respectively. A similar facilitatory effect on stepping was observed in response to drugs administered via either catheter. The results indicate that partial spontaneous recovery of stepping occurs in adult rats after abolishing all long direct bulbospinal connections, in contrast to previous studies suggesting that hindlimb stepping after dual hemisections either does not occur or is observed only if the second hemisection surgery is delayed relative to the first. The results support the hypothesis that artificial modulation of propriospinal neuron excitability may facilitate recovery of motor function after spinal cord injury. However, whether this facilitation is due to enhanced transmission of a descending locomotor signal or is the result of excitation of thoracolumbar circuits independent of supraspinal influence, requires further study.
authors.affiliation: Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada.
authors.forename: Kristine C
authors.initials: KC
authors.lastname: Cowley
authors.affiliation: Department of Physical Therapy, College of Rehabilitation Sciences, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: MacNeil
authors.affiliation: Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada.
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Chopek
authors.affiliation: Department of Radiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Sutherland
authors.affiliation: Department of Physiology and Pathophysiology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada; Department of Internal Medicine, Section of Neurology, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, R3E 3J7, Canada. Electronic address: brian@scrc.umanitoba.ca.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality / Q000187:drug effects; D020233:Gait Disorders, Neurologic / Q000188:drug therapy* / Q000209:etiology*; D006614:Hindlimb / Q000503:physiopathology; D016202:N-Methylaspartate / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011814:Quipazine / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use; D013116:Spinal Cord; D013119:Spinal Cord Injuries / Q000150:complications*; D013268:Stimulation, Chemical; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; D018377:Neurotransmitter Agents; D017366:Serotonin Receptor Agonists; D011814:Quipazine; D016202:N-Methylaspartate
keywords: Functional recovery; Hemisection; Locomotion; Neuroplasticity; Propriospinal; Rat; Spinal cord injury