Assessing Forelimb Function after Unilateral Cervical Spinal Cord Injury: Novel Forelimb Tasks Predict Lesion Severity and Recovery

Abstract

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. Recently there has been increasing interest in cervical spinal cord injury models because the majority of spinal cord injuries are at cervical levels. Here we examined spontaneous functional recovery of adult rats with either laminectomy or lateral hemisection of the cervical spinal cord at C3-C4. Behavioral tests were carried out, including the forelimb locomotor scale (FLS), a postural instability test (PIT), a pasta-handling test that has been used to assess forepaw digit function and latency to eat, forelimb use during vertical-lateral wall exploration in a cylindrical enclosure, and vibrissae-elicited forelimb placing tests. In addition, a forelimb step-alternation test was developed to assess functional recovery at 12 weeks post-injury. All tests detected cSCI-induced deficits relative to laminectomy. Interestingly, the severity of deficits in the forelimb step-alternation test was associated with more extensive spinal damage, greater impairment, and less recovery in the FLS and other tests. For the pasta-handling test we found that rats with a milder cervical injury (alternators) were more likely to use both forepaws together compared to rats with a more severe injury (non-alternators). In addition, using the PIT, we detected enhanced function of the good limb, suggesting that neural plasticity on the unaffected side of the spinal cord may have occurred to compensate for deficits in the impaired forelimb. These outcome measures should be useful for investigating neural events associated with cSCI, and for developing novel treatment strategies.

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“…Tests include the skilled paw-reaching staircase task [44][45][46] , pasta handling [47] , single-pellet retrieval [48,49] , ladder walking [50,51] , skilled walking and swimming [52,53] .…”

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

“…Animals within a study group should be approximately the same weight, size and age as large differences in body weight can result in variation in the baseline distance needed for maintaining center of gravity for a given animal 19 . A sham group should be included while using PIT to verify that changes in behavior are due to regeneration or recovery rather than age and weight gain.…”

“…The postural instability test (PIT) was previously described and used in animals with a rodent model of Parkinson's disease 18 and in a rodent model of cSCI 19 . We used PIT after cSCI and found that there was a significant effect of lesion status [F(1,1) = 8.17, p < 0.01].…”

“…A similar test has been used previously to detect deficits in skilled use of forelimbs in animal models of unilateral stroke and Parkinson's disease 20,21 and after cSCI 19 . At chronic time points after injury (12 weeks post-injury), all sham animals ate pasta using both paws during the test period.…”

“…There are several useful behavioral tests to assess forelimb function after cSCI in rodents [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] , however, many of these tests are difficult to use and require specialized equipment. Pasta handling tests have been developed by other groups 18,19 , but these tests require that the animals be filmed in specific pasta eating cages, which requires a long training period, while the method we propose can be performed in the animals' home cage. Previously described pasta tests require significant analysis time and often expensive software, unlike the test described here.…”