Influences of Glabridin Treatment on Motor Function Recovery after Spinal Cord Injury

SUMMARY: Spinal cord injury (SCI) usually arises from compression due to traffic accidents and falls, resulting in varying degrees of movement, sensory loss, and possible paralysis. Glabridin (Gla) is a natural compound derived from licorice. It significantly affects drug development and medicine because of its anti-inflammatory, anti-oxidative, anti-tumoral, antibacterial, bone protective, cardiovascular protective, neuroprotective, liver protective, anti-obesity, and anti-diabetic properties. Various methods were employed to administer Gla to SCI mice in order to investigate its impact on the recovery of motor function. The mice were allocated into four cohorts using a randomization procedure. In the sham cohort, solely the lamina of vertebral arch was surgically exposed without causing any harm to the spinal cord tissue. Conversely, the injury cohort was subjected to spinal cord tissue damage and received no treatment thereafter. The mice in the remaining two cohorts received a dosage of 40 mg/kg Gla every two days via either intraperitoneal or intrathecal injection for a duration of 42 d following spinal cord injury. We conducted behavioral tests utilizing the Basso Mouse Scale score and gait analysis techniques. Magnetic resonance imaging and hematoxylin and eosin were employed to evaluate scar tissue formation. Systemic inflammation in mice was evaluated by employing an enzyme-linked immunosorbent assay. Gla promoted motor function recovery in mice following SCI and improved the pathological environment in the damaged area. These alterations were more evident in mice subjected to the intrathecal injection method. Intraperitoneal injections appear to be more beneficial for controlling systemic inflammatory responses. Although more intensive studies are required, Gla exhibits promising clinical potential as a cost-effective dietary phytochemical.

La lesión de la médula espinal (LME) generalmente surge de la compresión producto de caídas y accidentes de tránsito, lo que resulta en alteraciones del movimiento, pérdida sensorial y posible parálisis. La Glabridina (Gla) es un compuesto natural derivado del regaliz, constituyéndose en un aporte significativo para el desarrollo de fármacos y la medicina debido a sus propiedades antiinflamatorias, antioxidantes, antitumorales, antibacterianas, osteoprotectoras, cardioprotectoras, neuroprotectoras, hepatoprotectoras, antidiabéticas y contra la obesidad. En el presente trabajo se emplearon varios métodos para administrar Gla a ratones con lesión medular con el fin de investigar su impacto en la recuperación de la función motora. Los ratones fueron distribuidos en cuatro grupos mediante un procedimiento de aleatorización. En el grupo simulado, únicamente se expuso quirúrgicamente la lámina del arco vertebral sin causar ningún daño al tejido de la médula espinal. Por el contrario, el grupo lesionado fue sometido a daño del tejido de la médula espinal, sin recibir tratamiento posterior. Los ratones de los dos grupos restantes recibieron una dosis de 40 mg/kg de Gla cada dos días mediante inyección intraperitoneal o intratecal durante 42 días después de la lesión de la médula espinal. Fueron realizadas pruebas de comportamiento utilizando la puntuación de la escala Basso Mouse y técnicas de análisis de la marcha. Se emplearon imágenes por resonancia magnética y se aplicaron tinciones histológicas (Hematoxilina & Eosina) en muestras para evaluar la formación de tejido cicatricial. La inflamación sistémica en ratones se evaluó mediante el empleo de un ensayo inmunoabsorbente ligado a enzimas. Gla promovió la recuperación de la función motora en ratones después de una lesión medular y mejoró el entorno patológico en el área dañada. Estas alteraciones fueron más evidentes en ratones sometidos al método de inyección intratecal. Las inyecciones intraperitoneales parecen ser más beneficiosas para controlar las respuestas inflamatorias sistémicas. Aunque se requieren estudios más intensivos, Gla exhibe un potencial clínico prometedor como fitoquímico dietético rentable.

Neuroprotective therapy for acute ischemic stroke in the era of endovascular therapy / 国际脑血管病杂志

In recent years, endovascular therapy has become the most important progress in the field of the treatment of acute ischemic stroke caused by large vessel occlusion. However, the vascular recanalization shown by imaging after endovascular treatment cannot fully translate into effective tissue reperfusion and functional outcome, a phenomenon known as "futile recanalization". Combined neuroprotective therapy after vascular recanalization is expected to reduce the occurrence of futile recanalization and improve the outcome of patients. This article briefly summarizes the main application progress of commonly used neuroprotective therapies in clinical practice (edaravone dexborneol, glucocorticoids, hypothermia, and remote ischemic conditioning). It explores the trend and direction of combining endovascular therapy and neuroprotective therapy for patients with acute ischemic stroke caused by large vessel occlusion, and provides further reference and suggestions for intervention measures after endovascular therapy.

Research Progress on Aerobic Exercise Intervention for Learning and Memory Ability in Chronic Cerebral Ischemia / 昆明医科大学学报

Active physical exercise can effectively alleviate the pathological process of chronic cerebral ischemia(CCH)and improve learning and memory ability.This paper reviews the possible biological mechanisms of aerobic exercise to delay the pathological process of chronic cerebral ischemia and improve learning and memory.Previous studies have found that aerobic exercise can improve the neuroprotective effect,enhance the plasticity of hippocampal synapses,improve the activity of the upper and lower pathways of hippocampal tissue,and improve learning and memory ability.However,the intervention effect of aerobic exercise on chronic cerebral ischemia should be fully considered at the intervention time,and the intervention effect is also different.

Effect of alisol A on cerebral ischemia reperfusion injury by protecting blood brain barrier and its mechanism / 中国药理学通报

Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol

The neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/reperfusion in rats / 中国药理学通报

Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.

Targeting ferroptosis for treatment of Alzheimer' s disease / 中国药理学通报

Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

Effect and mechanism of long-term indwelling needle at Baihui acupoint on improving neurological function in ischemic stroke mice / 中华老年心脑血管病杂志

Objective To investigate the effect and mechanism of long-term indwelling needle of Baihui acupoint during acupuncture on improving neurological function in ischemic stroke mice through brain-derived neurotrophic factor(BDNF)/tyrosine receptor kinase B(TrkB)pathway.Methods A total of 48 male C57BL/6J mice were randomly divided into sham group 1,model group 1,long-term indwelling needle group 1 and conventional indwelling needle group,with 12 mice in each group.A mouse model of ischemic stroke was established by thread occlusion in the latter 3 groups.From the first day after modeling,long-term and conventional indwelling needle at Baihui acupoint was given to the mice in the corresponding groups for 14 consecutive days.Anoth-er 40 male C57BL/6J mice were also subjected and randomly divided into sham group 2,model group 2,and long-term indwelling needle groups 2 and 3,with 10 mice in each group.After model-ing in the latter 3 groups,100 pl adeno-associated virus was injected by caudal vein before acu-puncture treatment.Modified neurological severity score(mNSS)and escape latency,residence time in the target quadrant,and times of crossing the original platform in water maze test were used to evaluate neural function.Results Decreased mNSS score,shorter residence time in the target quadrant,less times of crossing the original platform,and reduced expression levels of BDNF and TrkB in the ischemic brain tissue,and higher apoptotic rate and elevated level of cleaved Caspase-3 in the ischemic brain tissue were observed in the model group 1 when compared with the sham group 1(P＜0.05).While long-term and conventional indwelling needle could reverse above indicators,with long-term indwelling needle more significant than the conventional method(P＜0.05).The long-term indwelling needle group 3 obtained lower mNSS score,reduced residence time in the target quadrant,lower times of crossing the original platform and decreased levels of BDNF and TrkB in the ischemic brain tissue(P＜0.05),and higher apoptotic rate and elevated level of cleaved Caspase-3 in the ischemic brain tissue than the long-term indwelling nee-dle group 2[(16.41±2.25)％vs(7.59±1.09)％,1.46±0.16 vs 0.94±0.12,P＜0.05].Conclusion Long-term indwelling needle at Baihui acupoint more significantly improves the neurological func-tion in ischemic stroke mice than ordinary indwelling needle treatment.Its molecular mechanism is due to activating the BDNF/TrkB pathway.

Mechanism of lncRNA-N1LR in blood-brain barrier injury during cerebral ischemia reperfusion / 中华老年心脑血管病杂志

Objective To investigate the action mechanism of long non-coding RNA(lncRNA)-N1LR on blood-brain barrier(BBB)after cerebral ischemia-reperfusion(I/R)injury.Methods Primary rat brain microvascular endothelial cells(BMECs)were cultured and treated with OGD/R to simulate cerebral I/R injury.The experiment was divided into normal control group,ln-cRNA-N1LR OGD group,overexpression group(lncRNA-N1LR overexpression after OGD treat-ment)and silence group(lncRNA-N1LR silence after OGD treatment).The mRNA levels of ln-cRNA-N1LR,claudin-5 and occludin in each group were detected by RT-qPCR.The BBB permea-bility was detected by FITC-dextran infiltration assay.The expression of claudin-5 and occludin were detected by Western blotting.Results The mRNA levels of lncRNA-N1LR,occludin and claudin-5 were significantly decreased(0.31±0.01 vs 1.00±0.10,0.42±0.03 vs 1.01±0.13,0.38±0.03 vs 1.00±0.15,P＜0.05),and the BBB permeability was significantly increased(58.79± 3.04 vs 8.87±0.63,P＜0.05)in the OGD group than the control group.The lncRNA-N1LR over-expression group increased the mRNA expression of lncRNA-N1LR,occludin and claudin-5(0.67±0.07 vs 0.31±0.01,0.92±0.02 vs 0.42±0.03,0.70±0.08 vs 0.38±0.03,P＜0.05),and decreased the BBB permeability(41.57±2.43 vs 58.79±3.04,P＜0.05)than the OGD group.lncRNA-N1LR silence resulted in lower mRNA levels of lncRNA-N1LR,occludin and claudin-5(0.21±0.02 vs 0.31±0.01,0.31±0.03 vs 0.42±0.03,0.22±0.02 vs 0.38±0.03,P＜0.05),and enhanced BBB permeability(72.34±1.43 vs 58.79±3.04,P＜0.05)when compared with the OGD group.Conclusion Up-regulation of lncRNA-N1LR may play a neuroprotective role by reducing BBB permeability.

Study on the neuroprotective effect of curculigoside on rats with spinal cord injury / 中国药房

OBJECTIVE To investigate the neuroprotective effect of curculigoside （CUR） on rats with spinal cord injury （SCI） based on phosphatase and tensin homologue deleted on chromosome ten gene-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase Parkin signaling pathway. METHODS Taking male SD rats as subjects， 15 rats were randomly selected as sham operation group； the rest rats were chosen to establish SCI model by spinal cord impact method， and then were divided into model group， CUR low-dose group （36 mg/kg CUR， gavage）， CUR high-dose group （72 mg/kg CUR， gavage） and CUR high-dose+3- methyladenine （3-MA） group （72 mg/kg CUR， gavage+20 mg/kg autophagy inhibitor 3-MA， intraperitoneal injection）， with 15 rats in each group. Rats in each group were given corresponding liquid/normal saline， once a day， for 28 consecutive days. Basso- Beattie-Bresnahan （BBB） score and Rivlin inclined plate experiment were performed on the 14th and 28th day after administration； the pathological changes of spinal cord tissue in rats were observed in each group； the apoptosis of spinal cord tissue， the levels of oxidative stress factors [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）]， and the protein expressions of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， PINK1， Parkin， p62 and microtubule- associated protein light chain 3 （LC3） were all determined. RESULTS Compared with the sham operation group， obvious edema and bleeding in the spinal cord tissue of rats were observed in the model group， accompanied by a large number of inflammatory cell infiltration； BBB score and inclined plate angle， SOD and GSH levels， the protein expressions of BDNF， PINK1 and Parkin， and LC3Ⅱ/Ⅰ ratio were significantly reduced； the apoptosis rate， MDA level， the protein expressions of GFAP and p62 in spinal cord tissue were significantly increased （P＜0.05）. Compared with the model group， the edema， bleeding and infiltration of inflammatory cells in the spinal cord tissue of rats were reduced in the administration groups， and the above quantitative indicators had been significantly improved （P＜0.05）； 3-MA could significantly reverse the improvement effects of the above indexes by CUR （P＜0.05）. CONCLUSIONS CUR can promote the recovery of neurological and motor functions in SCI rats， improve the pathological injury of the spinal cord and inhibit apoptosis， which may be related to mitochondrial autophagy mediated by activating the PINK1/Parkin signaling pathway.

Recent advance in efferocytosis and stroke / 中华神经医学杂志

Stroke is a cerebrovascular disease with high incidence, disability rate, and recurrence. Researches in recent years discover that the clearance of dead cells, efferocytosis, plays a vital role in pathological process of stroke. This article reviews the research progress of relation between efferocytosis and stroke, in order to provide a new perspective for neuroprotective therapies after stroke.

Study on the protective effect of soybean phospholipid powder on nerve injury / 安徽医科大学学报

Objective @#To investigate the protective effects and mechanisms of soybean phospholipid powder on nerve cells in vitro and rats neural tissues.@*Methods @#In the cell experiments , the cytotoxicity of soybean phospholipid powder with different concentrations on mouse microglia cells ( BV2 ) and rat adrenal pheochromocytoma (PC12) cells was ob served by cell counting kit⁃8( CCK⁃8) assay. The effect of soybean phospholipid powder on the NO level of BV2 cells was analyzed by NO determination experiment , and the synaptic growth of PC12 cells was observed under the microscope. In the animal experiment , the cognitive dysfunction of rat was simulated by scopol⁃ ocampal tissue morphology and nerve cell density of scopolamine model mice were ob served by hematoxylin ⁃eosin staining (HE) staining.@*Results @#Soybean phospholipid powder had no obvious cytotoxicity on BV2 cells and PC12 cells within the concentration of 1 000 μg/ml. Compared with the control group , the NO secretion of BV2 cells pretreated with soybean phospholipid powder significantly decreased (P < 0. 01) , and the neuronal synapse growth of PC12 cells significantly increased (P < 0. 01) . In comparison to the model group , soybean phospholipid powder significantly improved the learning and memory ability of scopolamine model rats (P < 0. 05) , reduced the neuronal damage in dentate gyrus (DG) , cornu ammonis3 (CA3) , cornu ammonis1 (CA1) areas of hippocampus , and increased the density of nerve cells (P < 0. 001) .@*Conclusion @#Soybean phospholipid powder can play a neuroprotective role by reducing neuroinflammation and promoting neuronal synapse growth at the cellular level , and improve the learning and memory ability of rats with cognitive impairment , reduce hippocampal tissue damage.

Neuroprotective mechanism by which fenofibrate regulates superoxide dismutase 2 expression in transgenic C57BL/6J mice / 中国组织工程研究

BACKGROUND:Oxidative injury is considered to be one of the important factors of cerebral ischemia-reperfusion injury.Superoxide dismutase 2(SOD2)is a key mitochondrial antioxidant molecule,and fenofibrate can regulate the expression of SOD2 by activating peroxisome proliferator-activated receptor α. OBJECTIVE:To explore whether the mechanism of fenofibrate in the treatment of cerebral ischemia-reperfusion injury depends on the expression of SOD2. METHODS:The TALENs system was used to construct SOD2 transgenic mice.The transgenic mice were genotyped by PCR and DNA sequencing techniques.The expression of SOD2 protein in transgenic mice was detected by western blot assay.Wild-type and SOD2 transgenic mice were randomly divided into four groups:wild-type control group(n=6),wild-type fenofibrate group(n=6),SOD2 transgenic control group(n=5)and SOD2 transgenic fenofibrate group(n=5).A mouse model of middle cerebral artery occlusion was prepared using the suture-occlusion method.After 90 minutes of ischemia,the thread was removed to reperfuse cerebral blood flow for 30 minutes.A cerebral blood flow monitor was used to monitor local cerebral blood flow.Brain tissue slices were taken for 2,3,5-triphenyltetrazolium chloride staining to analyze the situation of cerebral infarction in each group. RESULTS AND CONCLUSION:After PCR and DNA sequencing analysis,nine SOD2+/+ transgenic mice were successfully constructed.After cerebral ischemia-reperfusion,the wild-type fenofibrate group showed partial recovery of cerebral blood flow and significantly reduced cerebral infarction volume compared with the wild-type control group(P<0.001).There was no significant difference in cerebral blood flow and cerebral infarction volume between the SOD2 transgenic fenofibrate group and the SOD2 transgenic control group.The SOD2 transgenic control was superior to the wild-type control group in terms of improving cerebral blood flow and cerebral infarction(P<0.001).There were also no significant differences in cerebral blood flow and cerebral infarction volume between the wild-type fenofibrate group and the SOD2 transgenic control group and between the wild-type fenofibrate group and the SOD2 transgenic fenofibrate group.To conclude,the expression of SOD2 is one of the mechanisms of fenofibrate in the treatment of cerebral ischemia-reperfusion injury.

Neuroprotective mechanism of nicotine in a mouse model of rotenone-induced Parkinson's disease / 中国组织工程研究

BACKGROUND:Studies have found that nicotine can activate the dopamine system,slowing the progression of Parkinson's disease,but the specific mechanism is still unclear.Research on the neuroprotective mechanism of nicotine in animal models of Parkinson's disease is lacking. OBJECTIVE:To investigate the neuroprotective effect of nicotine on rotenone-induced Parkinson's disease in mice. METHODS:Twenty-eight C57BL/6 mice were randomly divided into vehicle group,rotenone group,autophagy agonist group and nicotine group,with seven mice in each group.Dopaminergic nerve damage was induced by rotenone in C57BL/6 mice,and the autophagy agonist(rapamycin)or nicotine was given before modeling.The spatial exploration function of the mice was observed by open field test.Western blot and Q-PCR were used to detect the expression of α-synuclein,autophagy related factors Beclin-1 and P62,and apoptosis-related factors Bax,Bcl-2 and Cleaved-caspase3 in the nigra of each group.The deposition of mitochondria,autophagosomes and lipofuscin in nigra cells were observed by transmission electron microscopy.The survival of neurons was observed by Nissl staining.The expression of tyrosine hydroxylase was observed by immunofluorescence and immunohistochemical staining. RESULTS AND CONCLUSION:The open field test showed that the distance,average speed and time of movement were reduced in the rotenone group compared with the solvent group.Compared with the rotenone group,the exercise distance,average speed and exercise time of mice were increased in the nicotine group and autophagy agonist group(P＜0.05).The results of immunofluorescence and immunohistochemistry showed that the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase in the rotenone group decreased compared with that in the solvent group.Compared with the rotenone group,the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase were increased in the nicotine group and autophagy agonist group.Western blot and Q-PCR results showed that compared with the solvent group,the expressions of α-synuclein and P62 in the rotenone group were increased,while Beclin-1 expression was decreased(P＜0.05);compared with the rotenone group,the expression of α-synuclein and P62 decreased in the nicotine group and autophagy agonist group,and the expression of Beclin-1 increased(P＜0.05).Compared with the solvent group,the expressions of Bax and Cleaved caspase3 were increased and Bcl-2 expression was decreased in the rotenone group(P＜0.05);compared with the rothenone group,the expressions of Bax and Cleaved-caspase3 were decreased and the expression of Bcl-2 was increased in the nicotine and autophagy agonist groups(P＜0.05).To conclude,nicotine may have a dopaminergic neuroprotective effect on rotenone-induced Parkinson's disease mouse models by improving autophagy dysfunction and reducing apoptosis.

Research progress of berberine in the field of neuroprotection in ischemic stroke / 中国比较医学杂志

Berberine is a natural isoquinoline alkaloid that was initially used as a broad-spectrum antibacterial agent in clinical treatment of enteritis,peptic ulcers,chronic gastritis,pneumonia,and other diseases.In recent years,in-depth study of the pharmacological effects of berberine has provided increasing evidence that berberine has neuroprotective effects on ischemic stroke.In this review,we introduce the effect of berberine on risk factors of ischemic stroke and discuss the neuroprotective effects of berberine on various mechanisms of ischemic stroke in detail to provide a reference for clinical and basic research in this field.

Is Deep Hypothermic Cardiac Arrest Mandatory in Aortic Arch Surgeries?

ABSTRACT Cannulation strategies in aortic arch surgeries are a matter of immense discussion. Majority of time deep hypothermic circulatory arrest (DHCA) is the way out, but it does come with its set of demerits. Here we demonstrate a case with aortic arch dissection dealt with dual cannulation strategy in axillary and femoral artery without need for DHCA and ensuring complete neuroprotection of brain and spinal cord without hinderance of time factor. Inception of new ideas like this may decrease the need for DHCA and hence its drawbacks, thus decreasing the morbidity and mortality associated.

Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (

Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a; <EDGPIPP) from Bothrops jararaca snake, on oxidative stress-induced toxicity in neuronal PC12 cells and astrocyte-like C6 cells. Methods: Both cells were pre-treated for four hours with different concentrations of PRO-7a, submitted to H2O2-induced damage for 20 h, and then the oxidative stress markers were analyzed. Also, two independent neuroprotective mechanisms were investigated: a) L-arginine metabolite generation via argininosuccinate synthetase (AsS) activity regulation to produce agmatine or polyamines with neuroprotective properties; b) M1 mAChR receptor subtype activation pathway to reduce oxidative stress and neuron injury. Results: PRO-7a was not cytoprotective in C6 cells, but potentiated the H2O2-induced damage to cell integrity at a concentration lower than 0.38 μM. However, PRO-7a at 1.56 µM, on the other hand, modified H2O2-induced toxicity in PC12 cells by restoring cell integrity, mitochondrial metabolism, ROS generation, and arginase indirect activity. The α-Methyl-DL-aspartic acid (MDLA) and L-NΩ-Nitroarginine methyl ester (L-Name), specific inhibitors of AsS and nitric oxide synthase (NOS), which catalyzes the synthesis of polyamines and NO from L-arginine, did not suppress PRO-7a-mediated cytoprotection against oxidative stress. It suggested that its mechanism is independent of the production of L-arginine metabolites with neuroprotective properties by increased AsS activity. On the other hand, the neuroprotective effect of PRO-7a was blocked in the presence of dicyclomine hydrochloride (DCH), an M1 mAChR antagonist. Conclusions: For the first time, this work provides evidence that PRO-7a-induced neuroprotection seems to be mediated through M1 mAChR activation in PC12 cells, which reduces oxidative stress independently of AsS activity and L-arginine bioavailability.(AU)

Anti-inflammatory strategies for hepatic encephalopathy: preclinical studies / Estratégias anti-inflamatórias para encefalopatia hepática: estudos pré-clínicos

Abstract Hepatic encephalopathy (HE) is a potentially reversible neuropsychiatric syndrome. Often, HE causes cognitive and motor dysfunctions due to an acute or chronic insufficiency of the liver or a shunting between the hepatic portal vein and systemic vasculature. Liver damage induces peripheral changes, such as in the metabolism and peripheral inflammatory responses that trigger exacerbated neuroinflammation. In experimental models, anti-inflammatory strategies have demonstrated neuroprotective effects, leading to a reduction in HE-related cognitive and motor impairments. In this scenario, a growing body of evidence has shown that peripheral and central nervous system inflammation are promising preclinical targets. In this review, we performed an overview of FDA-approved drugs and natural compounds which are used in the treatment of other neurological and nonneurological diseases that have played a neuroprotective role in experimental HE, at least in part, through anti-inflammatory mechanisms. Despite the exciting results from animal models, the available data should be critically interpreted, highlighting the importance of translating the findings for clinical essays.

Resumo A encefalopatia hepática (EH) é uma síndrome neuropsiquiátrica potencialmente reversível. Muitas vezes a EH causa disfunções cognitivas e motoras devido à insuficiência do fígado ou por um desvio entre a veia porta hepática e a vasculatura sistêmica. O dano no fígado provoca alterações periféricas, como no metabolismo e nas respostas inflamatórias periféricas, que desencadeiam uma neuroinflamação exacerbada. Em modelos experimentais, estratégias anti-inflamatórias têm demonstrado efeitos neuroprotetores, levando a uma redução dos prejuízos cognitivos e motores relacionados à EH. Neste cenário, evidências crescentes têm mostrado a inflamação periférica e no sistema nervoso central como um promissor alvo pré-clínico. Nesta revisão, abordamos uma visão geral de drogas e compostos naturais aprovados pelo FDA para o uso no tratamento de outras doenças neurológicas e não neurológicas, que tiveram papel neuroprotetor na EH experimental, pelo menos em parte, através de mecanismos anti-inflamatórios. Apesar dos resultados empolgantes em modelos animais, os dados avaliados devem ser criticamente interpretados, destacando a importância da tradução dos achados para ensaios clínicos.

Cuidado desenvolvimental para recém-nascidos pré-termos: revisão de escopo / Atención del desarrollo de los recién nacidos pretérmino: revisión del alcance / Developmental care for preterm newborns: a scoping review

Objetivo: mapear como o cuidado desenvolvimental prestado aos recém nascidos pré-termos tem sido desenvolvido nas unidades de terapia intensiva neonatal com a finalidade de sintetizar as evidências científicas atuais. Métodos: revisão de escopo com busca realizada em novembro de 2022 nas bases MEDLINE, Biblioteca Virtual em Saúde, CINAHL, Embase e Web of Science. Foram incluídos estudos que retratavam o cuidado desenvolvimental nas unidades neonatais, nos últimos cinco anos, sem restrição de idioma. Resultados: incluíram-se sete artigos e os principais temas foram: contato pele a pele, controle do ruído e luminosidade, participação da família e sensibilização e treinamento da equipe. Conclusão: esses cuidados contribuem para o desenvolvimento neuropsicomotor do prematuro, melhoram a assistência e reduzem a morbimortalidade e o tempo de internação.

Objective: To map the evolution of developmental care provided to preterm newborns in Neonatal Intensive Care Units to synthesize current scientific evidence. Methods: Bibliographic search for a scoping review was conducted in November 2022 on the MEDLINE, Virtual Health Library, CINAHL, Embase and Web of Science databases. Studies discussing developmental care in neonatal units in the past five years, without language restriction, were included. Results: The scoping review included articles, whose main topics were skin-to-skin contact, noise and light control, family participation, and team awareness and training. Conclusion: Developmental care practices contribute to the neuropsychomotor development of preterm infants, improve care, reduce morbidity and mortality, and the length of hospitalization.

Objetivo: mapear cómo se ha desarrollado la atención del desarrollo brindada a los recién nacidos pretérmino en las unidades de cuidados intensivos neonatales para sintetizar la evidencia científica actual. Métodos: revisión de alcance realizada en noviembre de 2022 mediante búsquedas en las bases de datos MEDLINE, Biblioteca Virtual en Salud, CINAHL, Embase y Web of Science. Se incluyeron estudios que trataron la atención del desarrollo en unidades neonatales, en los últimos cinco años, sin restricción de idioma. Resultados: se incluyeron siete artículos y los temas principales fueron contacto piel con piel, control de luz y ruido, participación familiar y sensibilización y entrenamiento del equipo. Conclusión: estos cuidados contribuyen al desarrollo neuropsicomotor de los prematuros, mejoran la asistencia y reducen la morbimortalidad y la estancia hospitalaria.

The Neuroprotective Effects of Ginsenoside Rd Pretreatment in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury

ABSTRACT Introduction: Paraplegia may develop as a result of spinal cord ischemia-reperfusion injury in patients who underwent thoracoabdominal aortic surgery. The objective of this research is to determine the neuroprotective effects of ginsenoside Rd pretreatment in a rat model of spinal cord ischemia-reperfusion injury. Methods: Sprague-Dawley rats (n=36) were randomly assigned to three groups. The sham (n=12) and control (n=12) groups received normal saline orally. The Rd group (n=12) received ginsenoside Rd (100 mg/kg) orally 48 hours before the induction of spinal cord ischemia. Spinal cord ischemia was induced by aortic occlusion using a Fogarty balloon catheter in the Rd and control groups. A neurological assessment according to the motor deficit index and a histological evaluation of the spinal cord were performed. To evaluate the antioxidant activity of ginsenoside Rd, malondialdehyde levels and superoxide dismutase activity were determined. Further, the tissue levels of tumor necrosis factor-alpha and interleukin-1 beta were measured. Results: The Rd group showed significantly lower motor deficit index scores than did the control group throughout the entire experimental period (P<0.001). The Rd group demonstrated significantly greater numbers of normal motor neurons than did the control group (P=0.039). The Rd group exhibited decreased malondialdehyde levels (P<0.001) and increased superoxide dismutase activity (P=0.029) compared to the control group. Tumor necrosis factor-alpha and interleukin-1 beta tissue levels were significantly decreased in the Rd group (P<0.001). Conclusion: Ginsenoside Rd pretreatment may be a promising treatment to prevent ischemia-reperfusion injury in patients who undergo thoracoabdominal aortic surgery.

Polarization shift of microglia phenotype: therapeutic targets for ischemic stroke / 国际脑血管病杂志

Neuroinflammatory response may accelerate tissue damage after ischemic stroke and affect neuronal death and neurogenesis. Microglia are an important line of defense against central nervous system injury, which are rapidly activated after cerebral ischemia and exert their effects by releasing various inflammatory mediators. Therefore, promoting the transition of microglia from M1 phenotype to M2 phenotype or maintaining dynamic balance between the two during the inflammatory process after ischemic stroke may be the important therapeutic targets for reducing inflammation after cerebral ischemia.