PMC

Representative Nissl stained sections at 7-days post-stroke from stroke + vehicle-treatment (a), stroke + L655,708-treatment starting at the time of stroke (b) and stroke + L655,708-treatment starting from 3-days post-insult (c). Quantification of the stroke volume is shown in panel (d). Data are mean ± s.e.m. for n=4 per group, * = P≤0.05.

a–c, L655,708 treatment starting from 3-days post-stroke resulted in a dose-dependent improvement in functional recovery post-stroke. d–f, Gabra5^−/− and Gabrd^−/− mice also showed decreased motor deficits post-stroke. Functional recovery was assessed with forelimb (a, d) and hindlimb foot-faults (b, e), and on the forelimb asymmetry (c, f). Low-dose L655,708 = 200μg/kg/day per animal; high-dose L655,708 = 400μg/kg/day per animal. Data are ± s.e.m. *** = P≤0.001 stroke + vehicle vs Sham; + = P≤0.05, ## = P≤0.01, # = P≤0.001 vs stroke + vehicle.

a, Blocking GAT-1 (NO-711) produced a higher % increase in I_tonic after stroke; combined blockade of GAT-1 and GAT-3/4 (NO-711 + SNAP-5114) produced a substantial I_tonic increase in controls but only an increase equivalent to blocking GAT-1 alone after stroke. b,c, I_tonic in sequential drug applications. Note the lack of response to SNAP-5114 application in the post-stroke slice. d, L655,708 reduced I_tonic. e, L655,708 significantly decreased post-stroke I_tonic. f, Drug treatment reverted post-stroke I_tonic to near-control level (asterisk: P<0.05; n.s.: no significance, bar graphs represent mean ± s.e.m.).

a, Images showing the peri-infarct recording site. Whole-cell patch-clamp recordings were made from post-stroke brain slices, within 200μm of infarct (top left), from layer-2/3 (top right) pyramidal neurons (bottom panels). b, Box-plot (boxes: 25–75%, whiskers:10–90%, lines: median) showing significantly elevated tonic inhibition in peri-infarct cortex (asterisk: P<0.05; see for additional analyses). c,d, Representative traces showing tonic inhibitory currents in control and peri-infarct neurons, respectively. Tonic currents were revealed by the shift in holding currents after blocking all GABA_ARs with gabazine (>100μM). Cells were voltage-clamped at +10mV.