Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem’s potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery.

Cell transplantation therapy offers great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is unclear. We investigated the regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischaemic stroke. The quantities of human mesenchymal stem cell (hMSC) secreted brain-derived neurotrophic factor in vitro and of monocyte chemotactic protein-1 at day 7 in vivo were both significantly higher for young hMSC compared with old hMSC. Male Sprague-Dawley rats subjected to transient middle cerebral artery occlusion that received young hMSC (trans-arterially at 24 h after stroke) showed better behavioural recovery with prevention of brain atrophy compared with rats that received old hMSC. Histological analysis of the peri-infarct cortex showed that rats treated with young hMSC had significantly fewer microglia and more vessels covered with pericytes. Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment, which was more pronounced for young hMSC. Aging of hMSC may be a critical factor that affects cell therapy outcomes, and transplantation of young hMSC appears to provide better functional recovery through anti-inflammatory effects, vessel maturation, and neurogenesis potentially by the dominance of trophic factor secretion.

BACKGROUND AND PURPOSE: Identifying the precise hemodynamic features, including the fistulous point, is essential for treatments of dural arteriovenous fistulas (DAVFs). This study illustrates the efficacy of DynaCT digital angiograms obtained from a 3D C-arm CT to directly visualize the location of the fistulous points in DAVFs. MATERIALS AND METHODS: This retrospective study observed 14 consecutive patients with DAVFs, which included 7 cavernous sinuses, 4 transverse-sigmoid sinuses, 2 convexity-superior sagittal sinuses, and 1 tentorial sinus. In the assessment of the practical applicability for the diagnosis of DAVFs, images obtained from 2D digital subtraction angiography (DSA) and DynaCT were comparatively evaluated. RESULTS: In all patients, DynaCT digital angiography could clearly demonstrate the feeding arteries, the fistulous points, and the draining veins. Significant anatomic landmarks for the fistulous points with relationships to osseous structures were also provided. Compared with 2D DSA, DynaCT digital angiograms demonstrated 12 additional findings in 8 patients (57%), including the detection of the fistulous points (n = 7), the feeders (n = 1), the retrograde leptomeningeal drainage (n = 1), the draining veins (n = 1), and the venous anomaly (n = 2). CONCLUSIONS: In comparison with 2D DSA, DynaCT may provide more detailed information to evaluate DAVFs. DynaCT digital angiograms have a high contrast and isotropic spatial resolution, allowing a reliable visualization of small vessels and fine osseous structures. Such detailed information, especially for the location of the fistulous points, could be very useful for either the endovascular or the surgical treatments of DAVFs.

Background and Purpose—: The ivy sign on fluid-attenuated inversion recovery MRI is a specific finding in moyamoya disease (MMD). This sign indicates decreased cerebral perfusion, dilated pial vasculature, and slow leptomeningeal collateral flow. This study aimed to clarify the characteristics of perioperative changes in the ivy sign in relation to cerebral hyperperfusion, which frequently occurs in MMD of unknown pathogenesis. Methods—: This prospective study included patients with MMD who underwent superior temporal artery–middle cerebral artery single bypass. Fluid-attenuated inversion recovery MRI was performed to evaluate the appearance of the ivy sign in the ipsilateral hemisphere preoperatively and on postoperative days 2 and 30. The ivy sign was assessed in combination with perioperative symptoms and cerebral hemodynamics using single-photon emission computed tomography. Results—: Of 42 consecutive patients (55 sides) who underwent bypass surgery, 32 (58.2%) showed an increase in the ivy sign (de novo ivy sign) on postoperative day 2; this had disappeared by day 30. Interestingly, these 32 patients had a significantly higher incidence of hyperperfusion on single-photon emission computed tomography and hyperperfusion syndrome, and there was no correlation between the de novo ivy sign and a preoperative ivy sign or the preoperative cerebral hemodynamics. In multivariate analysis, a de novo ivy sign was significantly correlated with postoperative hyperperfusion. Conclusions—: In MMD, a de novo ivy sign could indicate postoperative hyperperfusion after bypass, which is not always correlated with preoperative hemodynamic impairment. Additional factors other than preoperative cerebral hemodynamics might be involved in postoperative hyperperfusion in MMD.