Recovery of an injured arcuate fasciculus via transcallosal fiber in a stroke patient: A case report.

RATIONALE: We report on a patient whose arcuate fasciculus (AF) and corticobulbar tract (CBT) recovered following an infarct in the middle cerebral artery (MCA) territory, demonstrated on serial diffusion tensor tractography (DTT). PATIENT CONCERNS: The patient showed moderate conduction aphasia on the Western Aphasia Battery with an aphasia quotient of 46.5‰ (spontaneous speech: 35.0‰, auditory comprehension: 36.0‰, and naming: 53.1‰) at 1 month after onset. His aphasia improved with an aphasia quotient of 49‰ (spontaneous speech: 71.0‰, auditory comprehension: 52.0‰, and naming: 59.0‰) at 10 months after onset. DIAGNOSIS: A 44-year-old right-handed male patient presented with aphasia and quadriplegia, which occurred at the onset of an infarct in the left MCA territory. INTERVENTION: Diffusion tensor imaging data were acquired twice (1 month and 10 months after onset). OUTCOMES: On one-month DTT, the discontinuation of the left AF and severe narrowing of the right CBT were observed. However, on ten-month DTT, the left AF was connected to the opposite AF by a new tract that passed through the splenium of corpus callosum, and the right CBT had become thicker. LESSONS: We believe that our results suggest a recovery mechanism of injured AF and CBT in stroke patients.

Combination of Electroacupuncture and Constraint-Induced Movement Therapy Enhances Functional Recovery After Ischemic Stroke in Rats.

Both electroacupuncture and constraint-induced movement therapy have been reported to produce therapeutic effects on the recovery of ischemic stroke. The combined use of these two therapies is not rare clinically, although its effectiveness is not yet clear. We aimed to evaluate the efficacy of the combination of electroacupuncture and constraint-induced movement therapy in ischemic stroke rats, and to explore the potential molecular mechanisms. Ischemic stroke rat models were established by middle cerebral artery occlusion. Then, the rats were assigned to receive one of the following interventions: sole electroacupuncture, sole constraint-induced movement therapy, the combination of both therapies, and no treatment. Functional recovery was assessed with the beam balance test and rotarod test. The infarct volume of the brain and the expression of the molecules Nogo-A, P75NTR, NGF, BDNF, and VEGF in the brain tissue were investigated. The results demonstrated that the combination of the two therapies significantly improved neurological functional recovery in ischemic stroke rats compared to each therapy alone (P < 0.01). We also observed a significant decrease in infarct volume in rats receiving the combined treatment. Nogo-A and P75NTR were downregulated and NGF, BDNF, and VEGF were upregulated in the combined treatment rats compared to the control rats. In conclusion, the combination of electroacupuncture and constraint-induced movement therapy enhanced functional recovery after ischemic stroke in rats, and it is a promising treatment strategy in the rehabilitation of stroke. The anti-Nogo-A effect of electroacupuncture may explain its good compatibility with CIMT in ischemic stroke rats.

Motor Function and Activities of Daily Living Recovery after Cardiogenic Internal Carotid Artery Infarction: A Retrospective Cohort study.

OBJECTIVES: this study determines recovery in physical activity and activities of daily living in the early stages after cardiogenic internal carotid artery infarction. MATERIALS AND METHODS: this retrospective comfort study compares assessment data for 334 patients: 150 patients had atherosclerotic infarction (67 internal carotid artery, 87 middle cerebral artery) and 180 had cardiogenic infarction (32 internal carotid artery infarction, 148 middle cerebral artery). We used Brunnstrom recovery score, posture assessment scale for stroke, and functional independence measure. RESULTS: on initial assessment, median Brunnstrom recovery for the cardiogenic internal carotid artery infarction group was I-II in the upper limb, I in the finger, I-II in the lower limb, and IV or higher in all other groups. The median Postural Assessment Scale for Stroke score for the cardiogenic internal carotid artery infarction group was 0; all other groups scored 14 or higher. The median Functional Independence Measure for the cardiogenic internal carotid artery infarction group was 18 (maximum of 100) and the median score for other infarct groups was 25-50 (maximum 126), with P < .01. After a month, final assessment results for the cardiogenic internal carotid artery infarction group were much lower than for the other groups. Only both internal carotid artery infarctions were compared. Atherosclerotic infarctions showed recovery across assessments, except understanding, onset, and memory (P < .01), and cardiogenic infarctions did not change from the initial assessment in all criteria assessed. CONCLUSIONS: adapting cardiogenic internal carotid artery infarction as a stroke recovery model is difficult.

Anti-spastic effect induced by waggle needling correlates with KCC2-GABAA pathway in post-stroke spasticity rats.

Although clinical efficacy of waggle needling has been confirmed, therapeutic mechanisms still remain poorly understood. Reduction of GABA was involved in the etiology of spasticity. Recently, accumulated evidences suggest that the inhibitory effect of GABA is determined by low intracellular chloride concentration, which is predominantly mediated by KCC2. This study was designed to investigate whether KCC2-GABAA pathway was involved in the mechanism underlying acupuncture intervention in rats with middle cerebral artery occlusion (MCAO). Three days after modeling, the rats received waggle needling, routine needling and placebo needling for 7 consecutive days. After treatment, the muscle spasticity, motor function and infarct volumes were tested. KCC2 and GABAAγ2 levels were detected via western blotting, RT-PCR and immunofluorescence. KCC2 antagonist and agonist were administered after the last intervention. We found that acupuncture, particularly waggle needling, could remarkably alleviate muscle spasticity, reverse motor deficits and reduce cerebral infraction in MCAO rats, possibly due to its effects on up-regulating expressions of KCC2 and GABAAγ2 in the cortical infarct regions. However, the effects were blocked by KCC2 antagonist. In summary, this study suggests that improvements in muscle spasticity and motor function induced by waggle needling correlates with the activation of KCC2-GABAA pathway.

Intensive treadmill training promotes cognitive recovery after cerebral ischemia-reperfusion in juvenile rats.

Rehabilitation training is routine for children who experience stroke, but its protective mechanism remains unclear. To study the effect of treadmill training intensity on hippocampal synaptic plasticity after cerebral ischemia, a model of middle cerebral artery occlusion (MCAO)/reperfusion was established in young rats to simulate childhood ischemic stroke. The rats were randomly allocated into five groups: sham operation, MCAO, low-intensity exercise and MCAO (5 m/min), medium-intensity exercise and MCAO (10 m/min), and high-intensity exercise and MCAO (15 m/min). Intervention was continued for 14 days, and a series of experimental tests were conducted. After MCAO, the juvenile rats exhibited a series of morphological and functional alterations, including changes in their neurobehavior and cerebral infarct volumes. Compared with control rats, MCAO rats had a longer escape latency and crossed fewer platforms in the water maze test and exhibited decreased hippocampal neuron density and Synapsin I and PSD95 expression. Furthermore, MCAO rats exhibited synapse morphology changes and abnormal serum levels of lactic acid and corticosterone. Treadmill training effectively reduced the neurobehavioral scores and cerebral infarction volumes, with medium-intensity training showing the best effect. Treadmill training shortened the escape latency, increased the number of platform crossings, and improved the spatial cognitive abilities of the rats, with the medium intensity training having the best effect on spatial learning/memory efficiency. Treadmill training increased the neuron density in the hippocampus, with the medium-intensity training resulting in the highest density. Treadmill training had a positive effect on the expression of Synapsin I and PSD95, with the medium-intensity training showing the strongest effect. Treadmill training improved the sub-microstructure synapse morphology, with the medium-intensity training demonstrating the best effect. Treadmill training increased the plasma levels of lactic acid and corticosterone, with the high-intensity training having the most obvious effect. Treadmill training can provide neuroprotection by promoting hippocampal synaptic plasticity, with medium-intensity training showing the most optimal effects.

Transcranial direct current stimulation treated by multilead brain reflex instrument accelerates neural functional recovery in a rat model of stroke.

PURPOSE: Clinical research suggests that transcranial direct current stimulation (tDCS) at bilateral supraorbital foramen and inferior orbital rim and nose intersections may facilitate rehabilitation after stroke. However, the underlying neurobiological mechanisms of tDCS remain poorly understood, impeding its clinical application. Here, we investigated the effect of tDCS applied after stroke on neural cells. MATERIALS AND METHODS: Middle cerebral arterial occlusion (MCAO) reperfusion was induced in rats. Animals with comparable infarcts were randomly divided into MCAO group and MCAO + tDCS group. Recovery of neurological function was assessed behaviorally by modified neurological severity score (mNSS). Ischemic tissue damage verified histologically by TTC and HE staining. Immunohistochemical staining, real-time qPCR, and western blot were applied to determine the changes of neural cells in ischemic brains. RESULTS: The results reveal that tDCS treated by multilead brain reflex instrument can promote the recovery of neurological function, remarkably reduce cerebral infarct volume, promote brain tissue rehabilitation, and can effectively inhibit astrocytosis and enhance neuronal survival and synaptic function in ischemic brains. CONCULSIONS: Our study suggests that tDCS treated by multilead brain reflex instrument could be prospectively developed into a clinical treatment modality.

Eating and Grooming Abilities Predict Outcomes in Patients with Early Middle Cerebral Infarction: A Retrospective Cohort Study.

Patients with cerebrovascular disorders are often forced to rest, with early prognosis made by bedside examination. However, overloading, for example, talking for a long time, may worsen the condition. We hypothesized that activities of daily living (ADL) from the Functional Independence Measure (FIM) that were actually performed regularly are useful to predict prognosis. The present study was aimed at determining the predictive items related to predicting prognosis from the status of early motor paralysis and ADL in patients with acute middle cerebral artery (MCA) infarction. We examined 367 patients with MCA infarction for Brunnstrom recovery stage (BRS) and FIM within 4 days of admission and modified the Rankin Scale before onset and just before discharge. Logistic regression analysis was used to compare two groups of patients based on their postdischarge destination (Home/another hospital or facility). The logistic regression analysis showed the following: BRS Hand: odds ratio (OR) 1.641 (95% CI 1.642 (1.336-2.017), p < 0.001); FIM Grooming: OR 1.279 (95% CI 1.220-1.807, p < 0.001); and FIM Eating: OR 1.280 (95% CI 1.102-1.488, p < 0.001). On the other hand, the ROC analysis showed the ROC area for Eating to be 0.830 (95% CI 0.787-0.874), for Grooming to be 0.81 (95% CI 0.765-0.865), and for BRS Hand to be 0.805 (95% CI 0.760-0.851). The BRS Hand and FIM Eating and Grooming domains were identified as predictive factors using the following cutoff points: BRS Hand stage V and FIM scores of 5 for Eating and 4 for Grooming. The cutoff points for the BRS Hand and FIM Eating revealed that, at a minimum, such patients can use the nonaffected hand. The presence of cognitive dysfunction or dysphagia affects these domains. Therefore, these results suggested that Eating and Grooming are appropriate as evaluation items.

Do All ASPECT Score Regions have the Same Predictive Power for Functional Outcomes?

BACKGROUND AND PURPOSE: ASPECTS (Alberta Stroke Program Early CT Score) is a 10-point topographic CT scan score that has been shown to be a strong prognostic factor in acute ischemic stroke. We investigated whether all ASPECTS regions have the same prognostic value. METHODS: Clinical characteristics, ASPECTS, and 3-month modified Rankin Scale (mRS) data were retrospectively collected in 350 patients who were diagnosed with middle cerebral artery (MCA) territory stroke. To describe the 3-month mRS data, an ordered categorical approach was applied using a proportional odds model. Furthermore, external validation was performed using additional data from 30 patients. RESULTS: As expected, ASPECTS was an independently important predictor. However, when 10 regions were analyzed separately, the M1, M2, and M3 regions, related to MCA cortex, were not found to predict 3-month mRS scores in the final model. The odds ratios for ischemic change in other regions (except M1, M2, and M3) ranged from 2.6 to 3.8. Moreover, among clinical characteristics, only age was identified as a significant predictor. The sensitivity and specificity of the final model in the external validation were 91% and 88%, respectively. CONCLUSIONS: All ASPECTS regions did not have the same predictive power for functional outcomes, defined as the 3-month mRS. The implementation of a proportional odds model allowed a proper description of the ordered categorical nature of the mRS and the identification of relevant predictors.

Willed­movement training reduces middle cerebral artery occlusion­induced motor deficits and improves angiogenesis and survival of cerebral endothelial cells via upregulating hypoxia­inducible factor­1α.

Willed movement facilitates neurological rehabilitation in patients with stroke. Focal ischaemia is the hallmark of patients after stroke, though the detailed molecular mechanism by which willed movement affects neurological rehabilitation after stroke is not fully understood. The aim of the present study was to dissect the key factors of the hypoxia signaling pathway responsible for the willed movement­improved rehabilitation. Sprague­Dawley rats undergoing right middle cerebral artery occlusion (MCAO) surgery were randomly divided into four groups: MCAO alone, willed movement (WM), environmental modification (EM) and common rehabilitation (CR). The neurological behaviour score was assessed, and infarction areas were detected by TTC staining. In addition, angiogenesis­associated genes (vascular epithelial growth factor, angiogenin­1, matrix metalloproteinases­2 and ­9) and hypoxia inducible factor (HIF)­1α expression was investigated in cells derived from MCAO, WM, EM and CR groups. Finally, the role of HIF­1α using HIF­1α knockdown in HUVECs under hypoxic conditions was evaluated. WM significantly improved neurological behaviour and rehabilitation by increasing the behaviour score and by decreasing the infarction area. In addition, CR, EM and WM raised the expression of angiogenesis­associated genes and HIF­1α, thereby promoting in vitro tube formation of primary endothelial cells. Knockdown of HIF­1α in HUVECs restored the increased expression of angiogenesis­associated genes to normal levels and inhibited in vitro tube formation of HUVECs. Willed movement most effectively improved the neurological rehabilitation of rats with focal ischaemia through upregulation of HIF­1α. The present findings provide insight into willed movement­facilitated rehabilitation and may help treat stroke­triggered motor deficit and improve angiogenesis of cerebral endothelial cells.

Power spectrum slope is related to motor function after focal cerebral ischemia in the rat.

Electroencephalography (EEG) changes across vigilance states have been observed after ischemic stroke in patients and experimental stroke models, but their relation to functional recovery remains unclear. Here, we evaluate motor function, as measured by single pellet reaching (SPR), as well as local EEG changes in nonrapid eye movement (NREM), rapid eye movement (REM), and wakefulness during a 30 day recovery period after middle cerebral artery occlusion or sham surgery in rats. Small cortical infarcts resulted in poor SPR performance and induced widespread changes in EEG spectra in the ipsilesional hemisphere in all vigilance states, without causing major changes in sleep-wake architecture. Ipsilesional 1-4 Hz power was increased after stroke, whereas power in higher frequencies was reduced, resulting in a steeper slope of the power spectrum. Microelectrode array analysis of ipsilesional M1 showed that these spectral changes were present on the microelectrode level throughout M1 and were not related to increased synchronization between electrodes. Spectrum slope was significantly correlated with poststroke motor function and may thus be a useful readout of recovery-related plasticity.

Postischemic Housing Environment on Cerebral Metabolism and Neuron Apoptosis after Focal Cerebral Ischemia in Rats.

The purpose of this study was to evaluate the roles of different housing environments in neurological function, cerebral metabolism, cerebral infarction and neuron apoptosis after focal cerebral ischemia. Twenty-eight Sprague-Dawley rats were divided into control group (CG) and cerebral ischemia group, and the latter was further divided into subgroups of different housing conditions: standard environment (SE) subgroup, individual living environment (IE) subgroup, and enriched environment (EE) subgroup. Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO). Beam walking test was used to quantify the changes of overall motor function. Cerebral infarction and cerebral metabolism were studied by in vivo magnetic resonance imaging and 1H-magnetic resonance spectra, respectively. Neuron necrosis and apoptosis were detected by hematoxylin-eosin and TUNEL staining methods, respectively. The results showed that performance on the beam-walk test was improved in EE subgroup when compared to SE subgroup and IE subgroup. Cerebral infarct volume in IE subgroup was significantly larger than that in SE subgroup (P<0.05) and EE subgroup (P<0.05) on day 14 after MCAO. NAA/Cr and Cho/Cr ratios were lower in MCAO groups under different housing conditions as compared to those in CG (P<0.05). NAA/Cr ratio was lower in IE subgroup (P<0.05) and higher in EE subgroup (P<0.05) than that in SE subgroup. NAA/ Cr ratio in EE was significantly higher than that in IE subgroup (P<0.05). Cho/Cr ratio was decreased in MCAO groups as compared to that in CG (P<0.05). A significant decrease in normal neurons in cerebral cortex was observed in MCAO groups as compared to CG (P<0.05). The amount of normal neurons was less in IE subgroup (P<0.05), and more in EE subgroup (P<0.05) than that in SE subgroup after MCAO. The amount of normal neurons in EE subgroup was significantly more than that in IE subgroup after MCAO (P<0.05). The ratio of TUNEL-positive neurons in EE was significantly lower than that in SE subgroup (P<0.05) and IE subgroup (P<0.05). Correlation analysis showed that the beam walking test was negatively correlated with NAA/Cr ratio (P<0.05). Cerebral infarct volume was negatively correlated with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.01). The amount of normal cortical neurons was positively correlated with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.05). The TUNEL-positive neurons showed a negative correlation with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.01). This study goes further to show that EE may improve neurological functional deficit and cerebral metabolism, decrease cerebral infarct volume, neuron necrosis and apoptosis, while IE may aggravate brain damage after MCAO.

The role of the ipsilesional side in the rehabilitation of post-stroke subjects.

Most stroke lesions occur in the middle cerebral artery territory, presenting a high probability of damage of pathways with predominant ipsilesional disposition, mainly related to postural control. Despite the high probability of bilateral postural control dysfunction based on neuroanatomical fundaments, both research and clinical rehabilitation involving stroke subjects have been focused on contralesional side (also named affected side) impairments, while ipsilesional side (also named non-affected side) impairments have been attributed to an adaptive strategy. This paper aims to present a critical understanding about the state-of-the-art that sustains the hypothesis that stroke subjects with middle cerebral artery territory lesion at the subcortical level show an atypical behaviour in the ipsilateral side associated with the lesion itself and the possible implications.

[Restoring of the speech functions in patients with aphasia in the early rehabilitation period of ischemic stroke]. / Vosstanovlenie rechevykh funktsii u bol'nykh s afaziei v rannem reabilitatsionnom periode ishemicheskogo insul'ta.

AIM: To study the efficacy of combined therapy including daily sessions and two 10-day injections of the drug cellex in patients with aphasia in the early rehabilitation period of ischemic stroke (II). MATERIAL AND METHODS: Forty patients in the early rehabilitation period of II in the basin of the left middle cerebral artery with moderate to severe aphasia were studied. Twenty patients received combined therapy, including daily sessions with a speech therapist-aphasiologist within 10 days using the improved method, then a self-study using educational materials and two 10-day injections of cellex. Other 20 patients received only speech therapy. To assess the efficacy of therapy, the automated "Program of examination of patients with aphasia", Goodglass-Kaplan scale, modified Rankin scale were used. RESULTS: There was a significant improvement of speech functions, communicative abilities and functional recovery (p<0.01) in patients of both groups. However, a significantly greater level of rehabilitation (p<0.05) was noted in patients treated with combined therapy included two courses of cellex. CONCLUSION: The results allow to recommend the inclusion of cellex in the complex rehabilitation of patients with post-stroke speech disorders.

Task-Specific Motor Rehabilitation Therapy After Stroke Improves Performance in a Different Motor Task: Translational Evidence.

While the stroke survivor with a motor deficit strives for recovery of all aspects of daily life movements, neurorehabilitation training is often task specific and does not generalize to movements other than the ones trained. In rodent models of post-stroke recovery, this problem is poorly investigated as the training task is often the same as the one that measures motor function. The present study investigated whether motor training by pellet reaching translates into enhancement of different motor functions in rats after stroke. Adult rats were subjected to 60-min middle cerebral artery occlusion (MCAO). Five days after stroke, animals received either training consisting of 7 days of pellet reaching with the affected forelimb (n = 18) or no training (n = 18). Sensorimotor deficits were assessed using the sticky tape test and a composite neuroscore. Infarct volumes were measured by T2-weighted MRI on day 28. Both groups of rats showed similar lesion volume and forelimb impairment after stroke. Trained animals improved in the sticky tape test after day 7 post-stroke reaching peak performance on day 14. More reaching attempts during rehabilitation were associated with a better performance in the sticky tape removal time. Task-oriented motor training generalizes to other motor functions after experimental stroke. Training intensity correlates with recovery.

Enhanced Motor Recovery After Stroke With Combined Cortical Stimulation and Rehabilitative Training Is Dependent on Infarct Location.

BACKGROUND: Cortical electrical stimulation of the motor cortex in combination with rehabilitative training (CS/RT) has been shown to enhance motor recovery in animal models of focal cortical stroke, yet in clinical trials, the effects are much less robust. The variability of stroke location in human patient populations that include both cortical and subcortical brain regions may contribute to the failure to find consistent effects clinically. OBJECTIVE: This study sought to determine whether infarct location influences the enhanced motor recovery previously observed in response to CS/RT. The efficacy of CS/RT to promote improvements in motor function was examined in 2 different rat models of stroke that varied the amount and location of cortical and subcortical damage. METHODS: Ischemic infarctions were induced by injecting the vasoconstricting peptide endothelin-1 either (1) onto the middle cerebral artery (MCA) producing damage to the frontal cortex and lateral striatum or (2) into a subcortical region producing damage to the posterior thalamus and internal capsule (subcortical capsular ischemic injury [SCII]). Daily CS/RT or RT alone was then given for 20 days, during which time performance on a skilled reaching task was assessed. RESULTS: Animals with MCA occlusion infarctions exhibited enhanced improvements on a skilled reaching task in response to CS/RT relative to RT alone. No such enhancement was observed in animals with SCII infarctions across the 20 days of treatment. CONCLUSIONS: The efficacy of CS for enhancing motor recovery after stroke may depend in part on the extent and location of the ischemic infarct.

Language specificity of lexical-phonological therapy in bilingual aphasia: A clinical and electrophysiological study.

Based on findings for overlapping representations of bilingual people's first (L1) and second (L2) languages, unilingual therapies of bilingual aphasia have been proposed to benefit the untrained language. However, the generalisation patterns of intra- and cross-language and phonological therapy and their neural bases remain unclear. We tested whether the effects of an intensive lexical-phonological training (LPT) in L2 transferred to L1 word production in a Persian-French bilingual stroke patient with Broca's aphasia. Language performance was assessed using the Bilingual Aphasia Test, a 144-item picture naming (PN) task and a word-picture verification (WPV) task. Electroencephalography (EEG) was recorded during PN and WPV in both languages before and after an LPT in French on a wordlist from the PN task. After the therapy, naming improved only for the treated L2 items. The naming performance improved neither in the untrained L2 items nor in the corresponding items in L1. EEG analyses revealed a Language x Session topographic interaction at 540 ms post-stimulus, driven by a modification of the electrophysiological response to the treated L2 but not L1 items. These results indicate that LPT modified the brain networks engaged in the phonological-phonetic processing during naming only in the trained language for the trained items.

Successful remote delivery of a treatment for phonological alexia via telerehab.

A growing body of literature supports the effectiveness of the remote delivery of rehabilitation services, i.e., telerehab. Aphasia treatment is particularly well suited for telerehab because of the verbal and visual nature of speech-language therapy, but scientific research investigating aphasia telerehab is in its infancy. No studies to date have evaluated whether treatment of acquired reading disorders by a live clinician can be feasibly, effectively, or efficiently conducted via telerehab. Here we address this gap in the literature by reporting our success remotely remediating the reading deficits of two participants with phonological alexia. We adapted for the telerehab setting a previously validated treatment for phonological alexia (Friedman, Sample, & Lott, 2002 ), which uses a paired-associate design to train reading of problematic words. Both telerehab participants significantly improved their reading of trained words in similar time frames as previous participants (Friedman et al., 2002 ; Kurland et al., 2008 ; Lott, Sample, Oliver, Lacey, & Friedman, 2008 ); furthermore, both participants reported high satisfaction with the telerehab setting. Although telerehab with alexic patients poses unique challenges, we conclude that treatment for alexia via telerehab is nevertheless feasible, may be equally effective as in-person treatment, and saves substantial resources for participants as well as clinicians.

Inhibition of interleukin-6 abolishes the promoting effects of pair housing on post-stroke neurogenesis.

Interleukin-6 (IL-6) has been shown to promote post-stroke angiogenesis and long-term functional recovery; however, whether IL-6 could promote post-stroke neurogenesis remains unclear. This study aims to investigate the effects of IL-6 on neurogenesis after ischemic stroke. We also investigated whether pair housing (PH) could improve the experimental stroke outcome through IL-6. Transient middle cerebral artery occlusion (tMCAO) was induced in mice treated with recombinant IL-6 (rIL-6) or anti-IL-6 neutralizing antibodies (anti-IL-6 mAbs). Another set of mice were pair-housed (PH; male and ovariectomized female) for 2weeks, subjected to tMCAO and then assigned to a housing condition (isolated or PH). Pair-housed mice were treated with anti-IL-6 mAbs. Behavioral assessments were made 3days before tMCAO and after 28 days of reperfusion. Neural progenitor cells (NPCs) isolated from ipsilateral subventricular zone (SVZ) at 14 days post-ischemia were treated with rIL-6 plus soluble IL-6 receptor (sIL-6R). The effects of IL-6 on the proliferation and differentiation of NPCs were examined in vivo and in vitro. The role and mechanism of IL-6 in PH-mediated enhancement of NPC proliferation and functional recovery were investigated in vivo. We found that anti-IL-6 mAbs significantly reduced the proliferation and neuronal differentiation of NPCs in the ipsilateral SVZ, as well as functional recovery; whereas rIL-6 conferred the opposite effects. PH significantly promoted NPC proliferation and functional recovery compared with socially isolated cohorts; blockade of IL-6 with anti-IL-6 mAbs prevented this promoting effect. In conclusion, our results suggest that IL-6 is an important mediator of social interaction on neurogenesis and long-term functional recovery after ischemic stroke.

Pulsed Transcranial Ultrasound Stimulation Immediately After The Ischemic Brain Injury is Neuroprotective.

GOAL: We applied a low-intensity pulsed transcranial ultrasound stimulation (pTUS) to the ischemic cortex after a distal middle cerebral artery occlusion (dMCAO) to study whether pTUS is capable of protecting brain from ischemic injury. METHODS: Rats were randomly assigned to Sham (n = 6), Control (n = 16), and pTUS (n = 16) groups. The pTUS-treated rats were subjected to 60-min ultrasonic stimulation immediately after the ischemia. After 48 h, the sensorimotor-related behavioral outcomes were assessed by a neurological severity score (NSS), and the permanent brain injury was assessed by the histologic analysis of TTC staining of brain slices. RESULTS: pTUS group showed significantly lower NSS (n = 10, 5.5 ± 2.5) than the Control group ( n = 10, 10.5 ±1.4) (p < 0.01). Concordantly, the ischemic lesion was significantly reduced after receiving pTUS immediately after dMCAO. The cortical infarct volume in the control group was more than threefold of the pTUS group (43.39% ± 2.33%, n = 16 versus 13.78% ± 8.18%, n = 16, p < 0.01). Immunohistochemical staining indicated reduction of neutrophils in the affected area, and laser speckle imaging showed significant increase of a cerebral blood flow after pTUS, which consistently supported the neuroprotection of pTUS in ischemic brain injury. CONCLUSION: Both behavior and histological results suggested that pTUS on ischemic core immediately after ischemic stroke could be neuroprotective. SIGNIFICANCE: The noninvasiveness and high spatiotemporal resolution of pTUS makes it a unique neuromodulation technique in comparison with the current TMS and tDCS.

The P300 in middle cerebral artery strokes or hemorrhages: Outcome predictions and source localization.

OBJECTIVES: There are no reliable outcome predictors for severely impaired patients suffering from large infarctions or hemorrhages within the territory of the middle cerebral artery. This study investigated whether the amplitude of the event-related potential (ERP) component P300 predicts if a patient will be transferred to the next stage of rehabilitation (positive outcome) or to a nursing home (negative outcome). The second goal was to look for lesion locations determining the generation of the P300 amplitude. METHODS: Forty-seven patients performed an auditory oddball task to elicit the P300 and were assessed with different scores for activities of daily living (ADL). Patients were divided in two groups according to their outcome. P300 amplitudes were compared between these groups controlling for age and gender. Post-hoc analyses were performed to analyse the relationship between P300 amplitude and neurological outcome scores. In addition, lesion overlaps were created to detect which lesion pattern affects P300 generation. RESULTS: Patients with a positive outcome showed higher P300 amplitudes at frontal electrode sites than those with a negative outcome. P300 amplitude correlated with ADL score difference. Lesions in the superior temporal gyrus, middle and inferior frontal and prefrontal regions led to visibly diminished P300 amplitudes. CONCLUSIONS: The findings suggest that an impairment of attention (P300 amplitude reduction) negatively influences successful neurological rehabilitation. Left superior temporal lobe and the left premotor/prefrontal areas are essential brain areas for the generation of the P300. SIGNIFICANCE: P300 amplitude may be used as an outcome predictor for severely impaired patients suffering from middle cerebral artery strokes or hemorrhages.