A narrative review of potential neural repair poststroke: Decoction of Chinese angelica and peony in regulating microglia polarization through the neurosteroid pathway.

Ischemic stroke is a major global health crisis, characterized by high morbidity and mortality rates. Although there have been significant advancements in treating the acute phase of this condition, there remains a pressing need for effective treatments that can facilitate the recovery of neurological functions. Danggui-Shaoyao-San (DSS), also known as the Decoction of Chinese Angelica and Peony, is a traditional Chinese herbal formula. It has demonstrated promising results in the regulation of microglial polarization and modulation of neurosteroid receptor expression, which may make it a potent strategy for promoting the recovery of neurological functions. Microglia, which plays a crucial role in neuroplasticity and functional reconstruction poststroke, is regulated by neurosteroids. This review posits that DSS could facilitate the recovery of neuronal function poststroke by influencing microglial polarization through the neurosteroid receptor pathway. We will further discuss the potential mechanisms by which DSS could enhance neural function in stroke, including the regulation of microglial activation, neurosteroid regulation, and other potential mechanisms.

Hypothermic neuroprotection by targeted cold autologous blood transfusion in a non-human primate stroke model.

Over decades, nearly all attempts to translate the benefits of therapeutic hypothermia in stroke models of lower-order species to stroke patients have failed. Potentially overlooked reasons may be biological gaps between different species and the mismatched initiation of therapeutic hypothermia in translational studies. Here, we introduce a novel strategy of selective therapeutic hypothermia in a non-human primate ischemia-reperfusion model, in which autologous blood was cooled ex vivo and the cool blood transfusion was administered at the middle cerebral artery just after the onset of reperfusion. Cold autologous blood cooled the targeted brain rapidly to below 34 °C while the rectal temperature remained around 36 °C with the assistance of a heat blanket during a 2-h hypothermic process. Therapeutic hypothermia or extracorporeal-circulation related complications were not observed. Cold autologous blood treatment reduced infarct sizes, preserved white matter integrity, and improved functional outcomes. Together, our results suggest that therapeutic hypothermia, induced by cold autologous blood transfusion, was achieved in a feasible, swift, and safe way in a non-human primate model of stroke. More importantly, this novel hypothermic approach conferred neuroprotection in a clinically relevant model of ischemic stroke due to reduced brain damage and improved neurofunction. This study reveals an underappreciated potential for this novel hypothermic modality for acute ischemic stroke in the era of effective reperfusion.

Mental stress, meditation, and yoga in cardiovascular and cerebrovascular diseases.

It is well known that stress can increase the risk of heart attack and stroke although the exact way it does this is unknown. This information is particularly more relevant in a post COVID-19 era where healthcare workers are increasingly facing more stressful working conditions. Thus, it is important to look into alternative methods to deal with stress including meditation and yoga which have shown potential.

Biphasic dose response in the anti-inflammation experiment of PBM.

Non-invasive laser irradiation can induce photobiomodulation (PBM) effects in cells and tissues, which can help reduce inflammation and pain in several clinical scenarios. The purpose of this study is to review the current literature to verify whether PBM can produce dose effects in anti-inflammatory experiments by summarizing the clinical and experimental effects of different laser parameters of several diseases. The so-called Arndt-Schulz curve is often used to describe two-phase dose reactions, assuming small doses of therapeutic stimulation, medium doses of inhibition, and large doses of killing. In the past decade, more and more attention has been paid to the clinical application of PBM, especially in the field of anti-inflammation, because it represents a non-invasive strategy with few contraindications. Although there are different types of lasers available, their use is adjusted by different parameters. In general, the parameters involved are wavelength, energy density, power output, and radiation time. However, due to the biphasic effect, the scientific and medical communities remain puzzled by the ways in which the application of PBM must be modified depending on its clinical application. This article will discuss these parameter adjustments and will then also briefly introduce two controversial theories of the molecular and cellular mechanisms of PBM. A better understanding of the extent of dualistic dose response in low-intensity laser therapy is necessary to optimize clinical treatment. It also allows us to explore the most dependable mechanism for PBM use and, ultimately, standardize treatment for patients with various diseases.

Normobaric Oxygen (NBO) Therapy Reduces Cerebral Ischemia/Reperfusion Injury through Inhibition of Early Autophagy.

OBJECTIVES: Normobaric oxygen (NBO) therapy has great clinical potential in the treatment of ischemic stroke, but its underlying mechanism is unknown. Our study aimed to investigate the role of autophagy during the application of NBO on cerebral ischemia/reperfusion injury. METHODS: Male Sprague Dawley rats received 2 hours of middle cerebral artery occlusion (MCAO), followed by 2, 6, or 24 hours of reperfusion. At the beginning of reperfusion, rats were randomly given NBO (95% O2) or room air (21% O2) for 2 hours. In some animals, 3-methyladenine (3-MA, autophagy inhibitor) was administered 10 minutes before reperfusion. The severity of the ischemic injury was determined by infarct volume, neurological deficit, and apoptotic cell death. Western blotting was used to determine the protein expression of autophagy and apoptosis, while mRNA expression of apoptotic molecules was detected by real-time PCR. RESULTS: NBO treatment after ischemia/reperfusion significantly decreased infarct volume and neurobehavioral defects. The increased expression of the autophagy markers, including microtubule-associated protein 1A light chain 3 (LC3) and Beclin 1, after ischemia/reperfusion was reversed by NBO, while promoting Sequestosome 1 (p62/SQSTM1) expression. In addition, NBO reduced cerebral apoptosis in association with alleviated BAX expression and increased BCL-2 expression. 3-MA reduced autophagy and apoptotic death but did not further improve NBO-attenuated ischemic damage. CONCLUSION: NBO induced remarkable neuroprotection from ischemic injury, which was correlated with blocked autophagy activity.

Neuroprotective Effects of Early Hypothermia Induced by Phenothiazines and DHC in Ischemic Stroke.

METHODS: Adult male Sprague Dawley rats were studied in 4 groups: (1) sham; (2) stroke; (3) stroke treated with pharmacological hypothermia before reperfusion (interischemia hypothermia); and (4) stroke treated with pharmacological hypothermia after reperfusion is initiated (inter-reperfusion hypothermia). The combination of chlorpromazine and promethazine with dihydrocapsaicin (DHC) was used to induce hypothermia. To compare the neuroprotective effects of drug-induced hypothermia between the interischemia and inter-reperfusion groups, brain damage was evaluated using infarct volume and neurological deficits at 24 h reperfusion. In addition, mRNA expressions of NADPH oxidase (NOX) subunits (gp91phox, p67phox, p47phox, and p22phox) and glucose transporter subtypes (GLUT1 and GLUT3) were determined by real-time PCR at 6 and 24 h reperfusion. ROS production was measured by flow cytometry assay at the same time points. RESULTS: In both hypothermia groups, the cerebral infarct volumes and neurological deficits were reduced in the ischemic rats. At 6 and 24 h reperfusion, ROS production and the expressions of NOX subunits and glucose transporter subtypes were also significantly reduced in both hypothermia groups as compared to the ischemic group. While there were no statistically significant differences between the two hypothermia groups at 6 h reperfusion, brain damage was significantly further decreased by interischemia hypothermia at 24 h. CONCLUSION: Both interischemia and inter-reperfusion pharmacological hypothermia treatments play a role in neuroprotection after stroke. Interischemia hypothermia treatment may be better able to induce stronger neuroprotection after ischemic stroke. This study provides a new avenue and reference for stronger neuroprotective hypothermia before vascular recanalization in stroke patients.

Detrimental and Beneficial Effect of Autophagy and a Potential Therapeutic Target after Ischemic Stroke.

Autophagy, a physiologic mechanism that promotes energy recycling and orderly degradation through self-regulated disassembly of cellular components, helps maintain homeostasis. A series of evidences suggest that autophagy is activated as a response to ischemia and has been well-characterized as a therapeutic target. However, the role of autophagy after ischemia remains controversial. Activated-autophagy can remove necrotic substances against ischemic injury to promote cell survival. On the contrary, activation of autophagy may further aggravate ischemic injury, causing cell death. Therefore, the present review will examine the current understanding of the precise mechanism and role of autophagy in ischemia and recent neuroprotective therapies on autophagy, drug therapies, and nondrug therapies, including electroacupuncture (EA).

General anesthesia vs local anesthesia during mechanical thrombectomy in acute ischemic stroke.

OBJECTIVE: To investigate the effect of general anesthesia (GA) on functional outcomes and complications rates in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT) compared to the use of local anesthesia (LA) at the puncture site. METHODS: This observational study was based on a prospectively registry study. AIS patients underwent MT with GA or LA from January 2013 to October 2017 were included. The primary outcome was the modified Rankin Scale (mRS) score at 90 days post-intervention. Furthermore, we assessed the long-term outcome of these patients. Multivariable logistic regression analysis was conducted to adjust for confounders. RESULTS: We enrolled 187 AIS patients in this study, patients in GA group had a similar mRS score compared to LA group at 90 days (2 [IQR, 1-4] vs 2.5 [IQR, 1-4], P = .917). No differences were found in the rates of functional independence (mRS 0-2), no or minimal disability (mRS 0-1), and mortality (mRS 6) between the 2 groups at 90 days post-intervention as well as long-term follow-up. The procedure-related complications and serious adverse events were similar between the LA group and GA group (P > .05 each). In multivariable analysis, GA use was not associated with functional outcomes. CONCLUSION: AIS patients who received GA during MT had similar functional outcomes and complications rates compared to patients received LA.

A mini review: garlic extract and vascular diseases.

Vascular diseases refer to medical conditions that narrow blood vessels. Narrowed cardiac or cerebral arteries can lead to myocardial infarction or ischemic stroke. Risk factors including atherosclerosis, hypertension, and diabetes may induce either cardiovascular or cerebral complications. Based on current research, garlic favorably affects atherosclerosis, hypertension and diabetes, and helps decrease the risk of myocardial infarction and ischemic stroke. Garlic has been utilized for hundreds of years as a natural health remedy. New research is emerging regarding its effectiveness in treating common diseases, including atherosclerosis, hypertension, and diabetes. The underlying mechanisms by which garlic, and its byproducts, can alter pathophysiology have begun to be elucidated by these studies. Garlic is a prominent topic for future research regarding its potential as an adjuvant to conventional pharmacotherapy for these common health conditions. In this mini-review, we discuss the current state of the literature regarding garlic and its effects in patients with vascular disease. Specifically, we decided to briefly discuss the key points regarding the mechanisms underlying garlic's anti-hypertensive, anti-hyperlipidemic, and hypoglycemic effects. This allows the readers to understand each process while keeping the paper concise. These mechanisms can be further explored in the original articles, at the reader's discretion.

Omega-3 fatty acid supplement reduces activation of NADPH oxidase in intracranial atherosclerosis stenosis.

Objectives Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide. We adapted a rat model of atherosclerosis to study brain intracranial atherosclerosis, and further investigated how omega-3 fatty acids (O3FA) attenuated the development of ICAS by reducing the generation of reactive oxygen species (ROS) and the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity. Methods Adult male Sprague-Dawley rats were divided into control normal-cholesterol or high-cholesterol diet groups with or without O3FA for up to 6 weeks. NG-nitro-L-arginine methyl ester (L-NAME, 3 mg/mL), a nitric oxide synthase inhibitor, was added to the drinking water of the high-cholesterol groups during the first 2 weeks. The rats received supplementation with O3FA (5 mg/kg/day) by gavage. At 3 and 6 weeks, we measured blood lipid levels, including low-density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG), and high-density lipoprotein (HDL) as atherosclerotic blood markers. The lumen of middle cerebral artery (MCA) and the thickness of the vessel wall were assessed histologically. ROS production was measured. NOX activity and mRNA and protein expression of NOX subunits (p47phox, gp91phox, p22phox, and p67phox) were measured. Results A high-cholesterol diet exhibited a significant increase in the classic blood markers (LDL, CHO, and TG) for atherosclerosis, as well as a decrease in HDL. These markers were found to be progressively more severe with time. Additionally, increased lumen stenosis and intimal thickening were observed in the MCA for this group. Rats given O3FA demonstrated attenuation of blood lipid levels with an absence of morphological changes.O3FA significantly reduced ROS production and NOX activity in the brain. Moreover, O3FA decreased the mRNA and protein expression of the NOX subunits p47phox, gp91phox, and p67phox. Conclusions Long-term O3FA dietary supplementation prevents the development of intracranial atherosclerosis. This O3FA effect appears to be mediated by its attenuation of NOX subunit expression and NOX activity, therefore reducing ROS production. O3FA dietary supplement shows promising results in the prevention of ICAS.

PM2.5 inhalation induces intracranial atherosclerosis which may be ameliorated by omega 3 fatty acids.

BACKGROUND: Intracranial atherosclerosis (ICA) a major health problem. This study investigated whether inhalation of fine airborne particulate matters (PM2.5) causes ICA and whether omega-3 fatty acids (O3FA) attenuated the development of ICA. RESULTS: Twelve but not 6 week exposure significantly increased triglycerides (TG) in normal chow diet (NCD), while PM2.5 enhanced all lipid profiles (TG, low density lipoprotein (LDL) and cholesterol (CHO)) after both 6 and 12-week exposure with high-cholesterol diet (HCD). PM2.5 exposure for 12 but not 6 weeks significantly induced middle cerebral artery (MCA) narrowing and thickening, in association with the enhanced expression of inflammatory cytokines, (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-γ)), vascular cell adhesion molecule 1 (VCAM-1) and inducible nitric oxide synthase (iNOS). O3FA significantly attenuated vascular alterations, even without favorable changes in lipid profiles, in association with reduced expression of IL-6, TNF-α, MCP-1, IFN-γ, VCAM-1 and iNOS in brain vessels. CONCLUSIONS: PM2.5 exposure for 12 weeks aggravates ICA in a dietary model (HCD + short-term L-NAME), which may be mediated by vascular inflammation. O3FA dietary supplementation prevents ICA development and inflammatory reaction in cerebral vessels. METHODS: Adult Sprague-Dawly rats were under filtered air (FA) or PM2.5 exposure with NCD or HCD for 6 or 12 weeks. Half of the HCD rats were treated with O3FA (5 mg/kg/day) by gavage. A total of 600 mg NG-nitro-L-arginine methyl ester (L-NAME, 3 mg/mL) per rat was administered over two weeks as supplementation in the HCD group. Blood lipids, including LDL, CHO, TG and high density lipoprotein (HDL), were measured at 6 and 12 weeks. ICA was determined by lumen diameter and thickness of the MCA. Inflammatory markers, IL-6, TNF-α, MCP-1, IFN-γ, VCAM-1 and iNOS were assessed by real-time PCR for mRNA and Western blot for protein expression.

Motor Imagery-Based Rehabilitation: Potential Neural Correlates and Clinical Application for Functional Recovery of Motor Deficits after Stroke.

Motor imagery (MI), defined as the mental implementation of an action in the absence of movement or muscle activation, is a rehabilitation technique that offers a means to replace or restore lost motor function in stroke patients when used in conjunction with conventional physiotherapy procedures. This article briefly reviews the concepts and neural correlates of MI in order to promote improved understanding, as well as to enhance the clinical utility of MI-based rehabilitation regimens. We specifically highlight the role of the cerebellum and basal ganglia, premotor, supplementary motor, and prefrontal areas, primary motor cortex, and parietal cortex. Additionally, we examine the recent literature related to MI and its potential as a therapeutic technique in both upper and lower limb stroke rehabilitation.

Experimental neuroprotection in ischemic stroke: a concise review.

Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. To date, intravenous tissue plasminogen activator and mechanical thrombectomy have been standards of care for AIS. There have been many advances in diagnostic imaging and endovascular devices for AIS; however, most neuroprotective therapies seem to remain largely in the preclinical phase. While many neuroprotective therapies have been identified in experimental models, none are currently used routinely to treat stroke patients. This review seeks to summarize clinical studies pertaining to neuroprotection, as well as the different preclinical neuroprotective therapies, their presumed mechanisms of action, and their future applications in stroke patients.

Omega-3 fatty acid supplement prevents development of intracranial atherosclerosis.

OBJECTIVES: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We adapted a rat model of atherosclerosis to study brain intracranial atherosclerosis, and further investigated the effect of omega-3 fatty acids (O3FA) in attenuating development of ICAS. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were divided into control normal-cholesterol or high-cholesterol diet groups with or without O3FA for up to 6weeks. During the first 2weeks, NG-nitro-l-arginine methyl ester (l-NAME, 3mg/mL) was added to the drinking water of the high-cholesterol groups. The rats received supplementation with O3FA (5mg/kg/day) by gavages. Blood lipids including low density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG) and high density lipoprotein (HDL) were measured at 3 and 6weeks. The lumen of middle cerebral artery (MCA) and the thickness of the vessel wall were assessed. Inflammatory molecular markers were assessed by Western blot. RESULTS: A high-cholesterol diet exhibited a significant increase in the classic blood markers (LDL, CHO, and TG) for atherosclerosis, as well as a decrease in HDL. These markers were found to be progressively more severe with time. Lumen stenosis and intimal thickening were increased in MCA. O3FA showed attenuation of blood lipids with an absence of morphological changes. O3FA significantly reduced the inflammatory marker CD68 in MCA and prevented monocyte chemotactic protein (MCP-1) and interferon-γ (IFN-γ) expression in the brain. O3FA similarly decreased inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6), markers affiliated with monocyte activity in atherosclerosis. Furthermore, O3FA significantly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1), a marker for endothelial activation. Lastly, O3FA increased ATP-binding cassette transporter A1 (ABCA1) protein expression via silent information regulator 1 (SIRT1) activation, thus increasing cholesterol efflux from macrophages to HDL. CONCLUSIONS: Long-term O3FA dietary supplementation prevents the development of intracranial atherosclerosis. This O3FA effect appears to be mediated by its prevention of macrophage infiltration into the vessel wall, therefore reducing inflammation and intimal thickening. While similar effects in humans need to be determined, O3FA dietary supplement shows promising results in the prevention of ICAS.

Music-supported therapy (MST) in improving post-stroke patients' upper-limb motor function: a randomised controlled pilot study.

OBJECTIVE: Music-supported therapy (MST) is a new approach for motor rehabilitation of stroke patients. Recently, many studies have demonstrated that MST improved the motor functions of post-stroke patients. However, the underlying mechanism for this effect is still unclear. It may result from repeated practice or repeated practice combined with musical stimulation. Currently, few studies have been designed to clarify this discrepancy. In this study, the application of "mute" musical instruments allowed for the study of music as an independent factor. METHODS: Thirty-three post-stroke patients with no substantial previous musical training were included. Participants were assigned to either audible music group (MG) or mute music group (CG), permitting observation of music's independent effect. All subjects received the conventional rehabilitation treatments. Patients in MG (n = 15) received 20 extra sessions of audible musical instrument training over 4 weeks. Patients in CG (n = 18) received "mute" musical instrument training of the same protocol as that of MG. Wolf motor function test (WMFT) and Fugl-Meyer assessment (FMA) for upper limbs were utilised to evaluate motor functions of patients in both groups before and after the treatment. Three patients in CG dropped out. RESULTS: All participants in both groups showed significant improvements in motor functions of upper limbs after 4  weeks' treatment. However, significant differences in the WMFT were found between the two groups (WMFT-quality: P = 0.025; WMFT-time: P = 0.037), but not in the FMA (P = 0.448). In short, all participants showed significant improvement after 4 weeks' treatment, but subjects in MG demonstrated greater improvement than those in CG. DISCUSSION: This study supports that MST, when combined with conventional treatment, is effective for the recovery of motor skills in post-stroke patients. Additionally, it suggests that apart from the repetitive practices of MST, music may play a unique role in improving upper-limb motor function for post-stroke patients.

Neuroprotection by peripheral nerve electrical stimulation and remote postconditioning against acute experimental ischaemic stroke.

OBJECTIVE: Local electrical stimulation (ES) was reported to protect the brain during ischaemic injury, while the protective effect of limb remote ischaemic postconditioning (RIPostC) was confirmed. The aim of this study was to explore whether remote peripheral nerve ES exerted neuroprotection and whether this procedure shared the same neuroprotective mechanism underlying RIPostC. METHODS: Stroke in Sprague-Dawley rats was induced by distal middle cerebral artery occlusion (dMCAO). Rats were divided into five groups: dMCAO, RIPostC, ES, nerve resection (NR) + ES and RIPostC+ES. Twenty-four hours after reperfusion, rats were examined for neurobehavioural function, including forelimb fault placing test, Ludmila Belayev 12 score test, and infarct volume. The expression of Bcl-2 and cleaved-caspase-3 in ischaemic cortex was assessed by Western blot. RESULTS: In forelimb fault placing test, as compared to the highest score in the stroke-only group, RIPostC, ES and RIPostC+ES groups showed a significantly (P < 0.01) lower score. The results were similar for the Ludmila Belayev 12 score test. The infarct volume of the treatment groups also exhibited significant (P < 0.01) reduction as compared to the stroke-only group. The volume of infarct tissue in the combination of RIPostC+ES was significantly less than RIPostC and ES alone (P < 0.05). Furthermore, NR blocked the ES's protection (P < 0.05) as compared to the ES group by using above-mentioned methods. Bcl-2 was upregulated, while cleaved-caspase-3 was downregulated in the experimental groups as compared to the control group. No difference was found among the experimental groups. DISCUSSION: Peripheral nerve ES appears to have a neuroprotective effect in a rat dMCAO model. This effect may indicate a neural protective mechanism underlying beneficial effect of RIPostC.

A Randomized Trial of Chinese Diaoshi Jifa on Treatment of Dizziness in Meniere's Disease.

Background. Meniere's disease is characterized by refractory dizziness and hearing disturbance. We aimed to investigate the efficacy and tolerance of Diaoshi Jifa, a Chinese hand skill for treating dizziness in Meniere's disease. Methods. An open-labeled, randomized, controlled intervention trial was conducted. Twenty-seven patients diagnosed with Meniere's disease were randomly allocated to control group or experimental group. Both groups were assessed by DHI (dizziness handicap inventory (DHI)) questionnaire score before and within 24 hours of receiving treatment, respectively. Results. Twenty-six participants completed the study, and no adverse event was reported due to Diaoshi Jifa treatment. The difference in the DHI scores between baseline and posttreatment reached significant difference in both groups (63.88 ± 19.94 versus 10.25 ± 9.77 and 54.36 ± 17.97 versus 49.6 ± 20.50). Significant difference in DHI scores was observed between the two groups after treatment (10.25 ± 9.77 versus 49.6 ± 20.50). Further investigation of DHI subscales in the experimental group revealed significant improvement posttreatment in the physical domain, functional domain, and emotional domain. Although higher rate of improvement in the emotional domain compared to physical or functional domains was found, the difference was not statistically significant. Conclusions. Diaoshi Jifa might be a fast, effective, and well-tolerated method for alleviating dizziness in Meniere's disease.

Hyperglycemia in stroke and possible treatments.

Hyperglycemia affects approximately one-third of acute ischemic stroke patients and is associated with poor clinical outcomes. In experimental and clinical stroke studies, hyperglycemia has been shown to be detrimental to the penumbral tissue for several reasons. First, hyperglycemia exacerbates both calcium imbalance and the accumulation of reactive oxygen species (ROS) in neurons, leading to increased apoptosis. Second, hyperglycemia fuels anaerobic energy production, causing lactic acidosis, which further stresses neurons in the penumbral regions. Third, hyperglycemia decreases blood perfusion after ischemic stroke by lowering the availability of nitric oxide (NO), which is a crucial mediator of vasodilation. Lastly, hyperglycemia intensifies the inflammatory response after stroke, causing edema, and hemorrhage through disruption of the blood brain barrier and degradation of white matter, which leads to a worsening of functional outcomes. Many neuroprotective treatments addressing hyperglycemia in stroke have been implemented in the past decade. Early clinical use of insulin provided mixed results due to insufficiently controlled glucose levels and heterogeneity of patient population. Recently, however, the latest Stroke Hyperglycemia Insulin Network Effort trial has addressed the shortcomings of insulin therapy. While glucagon-like protein-1 administration, hyperbaric oxygen preconditioning, and ethanol therapy appear promising, these treatments remain in their infancy and more research is needed to better understand the mechanisms underlying hyperglycemia-induced injuries. Elucidation of these mechanistic pathways could lead to the development of rational treatments that reduce hyperglycemia-associated injuries and improve functional outcomes for ischemic stroke patients.

Functional improvement after motor training is correlated with synaptic plasticity in rat thalamus.

The goals of this study were to determine whether functional outcome after motor training in rats was linked to synaptic plasticity in thalamus, and whether the Rota-rod apparatus, widely used to test motor function, could be used as an easy and quantitative motor skill training procedure. Adult female Sprague-Dawley rats (n = 39) were evaluated under three training conditions: 1. Movement requiring balance and coordination skills on Rota-rod; 2. simple exercise on treadmill; 3. nontrained controls. Motor function was evaluated by a series of motor tests (foot fault placing, parallel bar crossing, rope and ladder climbing) before and 14 or 28 days after training procedure. Synaptic strength in brain was assessed by synaptophysin immunocytochemistry. After 14 days of training, Rota-rod-trained animals significantly (p < 0.01) improved motor performance, compared to treadmill and nontrained animals. Animals with up to 28 days of simple exercises on the treadmill did not show a significantly improved performance on most motor tasks, except for an improvement in foot fault placing. Intensive synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus in Rota-rod-trained rats at 14 and 28 days, and in treadmill-trained rats at 28 days. The data suggested that functional outcome is effectively improved by motor skill training rather than by simple exercises, and this may be related, at least partially, to uniquely lateralized synaptogenesis in the thalamus. Both Rota-rod and treadmill could be quantitatively used in rats for motor training of different complexity.