Acute Neuromuscular Adaptation at the Spinal Level Following Middle Cerebral Artery Occlusion-Reperfusion in the Rat

International audienceThe purpose of the study was to highlight the acute motor reflex adaptation and to deepen functional deficits following a middle cerebral artery occlusion-reperfusion (MCAO-r). Thirty-six Sprague-Dawley rats were included in this study. The middle cerebral artery occlusion (MCAO; 120 min) was performed on 16 rats studied at 1 and 7 days, respectively (MCAO-D1 and MCAO-D7, n = 8 for each group). The other animals were divided into 3 groups: SHAM-D1 (n = 6), SHAM-D7 (n = 6) and Control (n = 8). Rats performed 4 behavioral tests (the elevated body swing test, the beam balance test, the ladder-climbing test and the forelimb grip force) before the surgery and daily after MCAO-r. H-reflex on triceps brachii was measured before and after isometric exercise. Infarction size and cerebral edema were respectively assessed by histological (Cresyl violet) and MRI measurements at the same time points than H-reflex recordings. Animals with cerebral ischemia showed persistent functional deficits during the first week post-MCAO-r. H-reflex was not decreased in response to isometric exercise one day after the cerebral ischemia contrary to the other groups. The motor reflex regulation was recovered 7 days post-MCAO-r. This result reflects an acute sensorimotor adaptation at the spinal level after MCAO-r

Infarct volume measurement from the Cresyl violet staining.

<p>The cerebral lesion size observed in the right hemisphere (RH) after MCAO-r was measured at D1 and D7. Values are expressed in % of the RH.</p

MRI analysis (T₂).

<p>Size of the cerebral edema at the right hemisphere after MCAO-r on 2 rats. The measures are realized at D1 and D7.</p

H_max/M_max ratios after isometric exercise.

<p>The M- and H-waves are evoked by stimulation of the musculospiral nerve. * indicates a significant decrease of H_max/M_max evoked after exercise compared to the H_max/M_max evoked before exercise for the Control, SHAM-D1, SHAM-D7 and MCAO-D7 groups (p<0.01). No difference was observed for the MCAO-D1 group.</p

Duration of isometric exercise evoked by electrical stimulation of the musculospiral nerve.

<p>+ indicates a significant difference between MCAO-D1 and MCAO-D7 groups compared to Control, SHAM-D1and SHAM-D7 groups (p<0.01).</p

Behavioral tests for Control, SHAM-D1 and MCAO-D1 groups.

<p>The PRE and D1 values are represented. ^* indicates significant differences between PRE and D1 (p<0.001). ⁺ indicates significant differences between MCAO-D1 group and the 2 other groups (p<0.001).</p

Beam balance test.

<p>The beam balance task is used to assess deficits of the vestibulomotor function after MCAOr. * indicates a significant decrease in the balance duration for MCAO-D7 group between PRE and from D1 to D7 (p<0.001). + indicates a significant decrease in the balance duration for MCAO-D7 group compared to Control and SHAM-D7 groups from D1 to D7 (p<0.001). For the MCAO-D7 group: Ω indicates a significant difference between D4 and D1 to D3; δ indicates a significant difference between D5 and D1 to D4; § indicates a significant difference between D6 and D1 to D4 (p<0,001 for all); ψ indicates a significant difference between D7 and D1 to D4 (p<0.001 for all).</p

Representative coronal slices with Cresyl violet following MCAO-r.

<p><b>A</b>. Slices recorded at MCAO-D1. <b>B</b>. Slices recorded at SHAM-D1.</p

Illustration of the behavioral tests.

<p><b>A</b>. The elevated body swing, <b>B</b>. The balance test on 2 wooden beams, <b>C</b>. The ladder-climbing test, <b>D</b>. The grip force test with both forelimbs and <b>E</b>. The grip force test with only one forelimb (in this example, the right forelimb).</p

The ladder-climbing test.

<p>The ladder-climbing test is used to evaluate the sensorimotor capacities to correctly grip the rung while rats climbed up a inclined ladder. <b>*</b> indicates a decrease of the successful score in the MCAO-D7 group between PRE and D1 to D7 (p<0.001). The successful score is expressed in % in the graph. <b>+</b> indicates a decrease of the successful score in the MCAO-D7 group compared to Control and SHAM-D7 groups from D1 to D7 (p<0.001). For the MCAO-D7 group: δ indicates a significant difference between D7 and D1 to D5; <b>§</b> indicates a significant difference between D6 and D1 to D5; ψ indicates a significant difference between D5 and D1 to D4 (p<0.001).</p