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Recovery of Functions after Spinal Cord Injury in Bonnet Macaques: Behavioral Analysis, pp. 1-131 $100.00
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. 


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Recovery of Functions after Spinal Cord Injury in Bonnet Macaques: Behavioral Analysis, pp. 1-131