Unilateral Frontal Lobe Contusion and Forelimb Function: Chronic Quantitative and Qualitative Impairments in Reflexive and Skilled Forelimb Movements in Rats

Abstract

Traumatic brain injury induced by mechanical impacts of the head can be modeled in rats in order to investigate acute and chronic therapy. Because frontal lobe contusion affects the neural representation of the forelimb in both the neocortex and basal ganglia, the purpose of the present experiments was to examine the chronic changes in reflexive and skilled forelimb induced by the injury. Contusions produced a cavity in the sensorimotor cortex, accompanied by shrinkage of the pyramidal tract, loss of cells in the dorsolateral striatum, and enlargement of the lateral ventricle. There were substantial individual differences in lesion size despite use of two different contusion forces, but all rats receiving contusions displayed chronic forelimb deficits. Reflexive tests of forelimb use (limb posture, placing, and support) indicated that impairments were most pronounced in the forelimb contralateral to the lesion. Tests of limb preference indicated that the contusion rats displayed a forelimb asymmetry: they were more likely to lean on their ipsilateral-to-lesion forelimb for support when rearing in a test cylinder, and this impairment was amplified in a home cage test. They also displayed a preference for the forelimb ipsilateral to the lesion when reaching for food, although both forelimbs were equally impaired on measures of success when reaching for food from a tray and reaching for a single food pellet on a shelf. A qualitative analysis from frame-by-frame video records indicated that when reaching for single pellets, impairments in forelimb use primarily affected the contralateral-to-lesion limb, especially limb aiming, supination, and food pellet release. Impairments in the ipsilateral-to-lesion forelimb were generally, but not exclusively, secondary to postural abnormalities. The wide range of chronic impairments in forelimb use following contusion injuries are discussed in relation to the anatomical and behavioral origins of the impairments and the potential use of forelimb tests in the assessment of therapy for traumatic brain injury to the frontal cortex.

Abnormalities in skilled reaching movements are improved by peripheral anesthetization of the less-affected forelimb after sensorimotor cortical infarcts in rats

“…By Day 32, rats had returned to pre-lesion reaching success levels with the contralesional forelimb. However, analysis using Whishaw's rating scale of reaching movements revealed movement abnormalities compared to the shamoperated group at this time point, also consistent with previous findings [16,55,57]. Anesthetization of the ipsilesional/non-preferred forelimb at this stage partially normalized movements in the other limb on this rating scale in both groups of rats.…”

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

“…Even though the initial loss in forelimb performance steadily corrected, the CCI animals never reached baseline performance, indicating persistent and perhaps chronic forelimb deficits. Our results are similar to those of a CCI study by Whishaw and associates, who also found chronic deficits in forelimb use (Whishaw et al, 2004). Based on their CCI parameters, the contusion likely included not only the CFA, but also the RFA (see Fig.…”

“…This result is not surprising in light of a previous study that found no group differences in lesion volume or behavioral deficits after contusion injuries, using an even wider range of impactor tip sizes, but with an impact depth similar to that used in our study (Whishaw et al, 2004). In both rat and mouse CCI models, tissue damage and severity of behavioral deficits are generally related to impact depth (Dixon et al, 1991;Feeney et al, 1982;Mao et al, 2010;Saatman et al, 2006), rather than tip diameter.…”

“…The rat was held in a suspended position facing the corner of a flat surface. Then it was gently moved closer to the corner from the lateral side until either the vibrissae (vibrissae-forelimb placing) or the forelimb (forelimb-forelimb placing) made contact with the surface (Whishaw et al, 2004). For normal performance (lifting the forelimb ipsilateral to the side being stimulated before forced contact), a score of ''1'' was recorded.…”

“…Based on their CCI parameters, the contusion likely included not only the CFA, but also the RFA (see Fig. 1 in Whishaw et al, 2004). The similarity in outcome indicates that sparing the RFA did not preclude the chronic deficits, and that a more focal CCI that spares the RFA can result in a similar consequence for skilled forelimb use.…”