Recovery of Functions after Spinal Cord Injury in Bonnet Macaques: Behavioral Analysis, pp. 1-131
Authors: R. Suresh Babu, Shubhangee Mungre, Jeffrey H. Kordower, Gowri Sethu, D. Sridevi, P. Periasamy and A. Namasivayam
Abstract: Damage to the spinal cord usually results in a loss of sensory and motor signals below the site of injury. Although no effective regeneration has been observed in the totally injured spinal cord, a wide range of spontaneous sensory-motor recovery can be achieved in adult mammals after an incomplete spinal cord injury. A number of approaches have been used to enhance axonal regeneration and analyze the improvement in recovery of spinal cord functions. In the present chapter, we have reviewed various experimental methods used to inflict injuries to the spinal cord in different animal models. We also discuss different behavioral techniques used to evaluate the degree of impairments or recovery of spinal cord functions in animals following the injury. Behavioral responses in animal models of spinal injury are a chief measure of determining the functional consequences of the spontaneous recovery of functions. The effectiveness of established and new therapeutic strategies based on the behavioral responses of animal models shows future promise in the treatment of spinal cord dysfunctions in patients. Most of the earlier work on quantitative evaluation of spontaneous recovery of locomotion after spinal cord injury has centered on behavioral tests and scoring techniques in rat models. However, there is a dearth of knowledge on behavioral analysis of sensory and motor recovery in nonhuman primate models. Analysis of gait function in quadrupedal animal model like rodents presents certain challenges in translation of animal behavior to humans. A quadrupedal animal model may mask the real status of hindlimb activities after inflicting spinal cord lesion. For instance, rats initially exhibit limited hindlimb movements after inflicting lower thoracic spinal lesions, and subsequently become proficient at partially supporting their body weight and move forward by pulling themselves with their forelimbs on a runway. Although some of the experiments on rats have led to clinical trials, it would appear imperative to use nonhuman primates such as macaque monkeys in order to relate experimental observations to recovery of functions in humans. Macaque monkeys are a suitable animal model for these studies as they exhibit a superior learning ability, extensive range of behavioral responses and sensory-motor capabilities compared to that of the rats and cats, and provide relevant information on the clinical signs seen in human patients. In this chapter, we will describe some of the experimental evidences in spinal cord injury research concerning the degree of spontaneous recovery in sensory and motor functions of macaque monkeys after inflicting spinal cord hemisection lesion. To our knowledge, this is the first report on spontaneous recovery of functions using macaque monkeys as a bipedal model. Briefly, we conducted investigations of three different types of behavioral outcomes in trained monkeys for this study: (i) analysis of the recovery of sensory function by establishing certain conditioned reflexes (viz., 2-point tactile discrimination test, direction of movement detection test and vibration sense test) in blindfolded condition to avoid visual guidance; (ii) quantitative analysis of the extent and time course of spontaneous recovery of bipedal locomotion following hemisection lesion using a battery of simple and complex locomotor tests (viz., narrow beam, grid, treadmill); and (iii) application of the footprint analyzing technique to reveal deficits in bipedal locomotor function that may not be apparent to the naked eye. The four gait variables used for footprint analysis were the following: tip of opposite foot, print length, total toe-spread, and intermediary toe spread. The variables in combination with other skilled behavioral tests were used in order to obtain additional information on the recovery of hindlimb function in a bipedal primate model. In addition, the data obtained was compared to earlier published work on the recovery of quadrupedal locomotion of spinally injured rodents. We find that the mechanisms underlying spontaneous recovery of functions in spinal cord lesioned macaques may be correlated to the mature function of spinal pattern generator for locomotion under the impact of residual descending and afferent connections. Further, this study also emphasizes the functional contribution of progressive strengthening of undamaged nerve fibers through a collateral sprouts/synaptic plasticity formed in partially lesioned cord of macaques.