Environmental Enrichment Protects Against Cognition Deficits Caused by Sepsis-Associated Encephalopathy.

BACKGROUND: One of the most serious complications of sepsis is sepsis-associated encephalopathy (SAE), which impairs the cognition ability of survivors. Environmental enrichment (EE) has been demonstrated to alleviate cognition deficits under many kinds of brain injury conditions. However, EE's effects on SAE remain unknown. Therefore, this study aimed to determine EE's effect on cognition disorders under SAE conditions and the underlying mechanism. MATERIALS AND METHODS: Adult male rats, subject to SAE or not, were housed under a standard environment (SE) or EE for 30 days. Subsequently, the rats were subjected to cognitive tests, such as the novel object recognition (NOR) test, the Morris water maze (MWM) test, an Open Field (OF) test, the elevated plus maze (EPM) test, and a sensory neglect (SN) test. Neuroinflammation, apoptosis, and oxidative stress changes in the brain were also detected. RESULTS: The results revealed that SAE impaired somatesthesia, recognition memory, spatial learning and memory, and exploratory activity, which were significantly improved by EE housing. EE also prevented SAE-induced anxiety-like behavior. In addition, EE housing capable induced a decrease in pro-inflammatory cytokines, and an increase in anti-inflammatory cytokines and antioxidant properties in the brain. Moreover, EE housing exerted an anti-apoptosis function by upregulating the level of B-cell lymphoma/leukemia-2 (Bcl-2) level and downregulating the level of p53 level in the hippocampus. CONCLUSIONS: The results of the present study indicated that EE exerts a neuroprotective function on cognitive ability in SAE rats. The effect is achieved by increasing antioxidants, and anti-inflammatory and antiapoptotic capacities. EE can effectively rescue SAE-induced cognitive deficits.

Infectious disease-associated encephalopathies.

Infectious diseases may affect brain function and cause encephalopathy even when the pathogen does not directly infect the central nervous system, known as infectious disease-associated encephalopathy. The systemic inflammatory process may result in neuroinflammation, with glial cell activation and increased levels of cytokines, reduced neurotrophic factors, blood-brain barrier dysfunction, neurotransmitter metabolism imbalances, and neurotoxicity, and behavioral and cognitive impairments often occur in the late course. Even though infectious disease-associated encephalopathies may cause devastating neurologic and cognitive deficits, the concept of infectious disease-associated encephalopathies is still under-investigated; knowledge of the underlying mechanisms, which may be distinct from those of encephalopathies of non-infectious cause, is still limited. In this review, we focus on the pathophysiology of encephalopathies associated with peripheral (sepsis, malaria, influenza, and COVID-19), emerging therapeutic strategies, and the role of neuroinflammation.

Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries: A call for action.

Although low- and middle-income countries (LMICs) shoulder 90 % of the neonatal encephalopathy (NE) burden, there is very little evidence base for prevention or management of this condition in these settings. A variety of antenatal factors including socio-economic deprivation, undernutrition and sub optimal antenatal and intrapartum care increase the risk of NE, although little is known about the underlying mechanisms. Implementing interventions based on the evidence from high-income countries to LMICs, may cause more harm than benefit as shown by the increased mortality and lack of neuroprotection with cooling therapy in the hypothermia for moderate or severe NE in low and middle-income countries (HELIX) trial. Pooled data from pilot trials suggest that erythropoietin monotherapy reduces death and disability in LMICs, but this needs further evaluation in clinical trials. Careful attention to supportive care, including avoiding hyperoxia, hypocarbia, hypoglycemia, and hyperthermia, are likely to improve outcomes until specific neuroprotective or neurorestorative therapies available.

NK-lysin peptides ameliorate viral encephalopathy and retinopathy disease signs and provide partial protection against nodavirus infection in European sea bass.

Antimicrobial peptides (AMP) comprise a wide range of small molecules with direct antibacterial activity and immunostimulatory role and are proposed as promising substitutes of the antibiotics. Additionally, they also exert a role against other pathogens such as viruses and fungi less evaluated. NK-lysin, a human granulysin orthologue, possess a double function, taking part in the innate immunity as AMP and also as direct effector in the cell-mediated cytotoxic (CMC) response. This molecule is suggested as a pivotal molecule involved in the defence upon nervous necrosis virus (NNV), an epizootic virus provoking serious problems in welfare and health status in Asian and Mediterranean fish destined to human consumption. Having proved that NK-lysin derived peptides (NKLPs) have a direct antiviral activity against NNV in vitro, we aimed to evaluate their potential use as a prophylactic treatment for European sea bass (Dicentrarchus labrax), one of the most susceptible cultured-fish species. Thus, intramuscular injection of synthetic NKLPs resulted in a very low transcriptional response of some innate and adaptive immune markers. However, the injection of NKLPs ameliorated disease signs and increased fish survival upon challenge with pathogenic NNV. Although NKLPs showed promising results in treatments against NNV, more efforts are needed to understand their mechanisms of action and their applicability to the aquaculture industry.

DL-3-n-butylphthalide-induced neuroprotection in rat models of asphyxia-induced cardiac arrest followed by cardiopulmonary resuscitation.

Most patients that resuscitate successfully from cardiac arrest (CA) suffer from poor neurological prognosis. DL-3-n-butylphthalide (NBP) is known to have neuroprotective effects via multiple mechanisms. This study aimed to investigate whether NBP can decrease neurological impairment after CA. We studied the protective role of NBP in the hippocampus of a rat model of cardiac arrest induced by asphyxia. Thirty-nine rats were divided randomly into sham, control, and NBP groups. Rats in control and NBP groups underwent cardiopulmonary resuscitation (CPR) 6 min after asphyxia. NBP or vehicle (saline) was administered intravenously 10 min after the return of spontaneous circulation (ROSC). Ultrastructure of hippocampal neurons was observed under transmission electron microscope. NBP treatment improved neurological function up to 72 h after CA. The ultrastructural lesion in mitochondria recovered in the NBP-treated CA model. In conclusion, our study demonstrated multiple therapeutic benefits of NBP after CA.

Polyethylene glycol-20k reduces post-resuscitation cerebral dysfunction in a rat model of cardiac arrest and resuscitation: A potential mechanism.

Out-of-hospital cardiac arrest (CA) is a leading cause of death in the United States. Severe post-resuscitation cerebral dysfunction is a primary cause of poor outcome. Therefore, we investigate the effects of polyethylene glycol-20k (PEG-20k), a cell impermeant, on post-resuscitation cerebral function. Thirty-two male Sprague-Dawley rats were randomized into four groups: 1) Control; 2) PEG-20k; 3) Sham control; 4) Sham with PEG-20k. To investigate blood brain barrier (BBB) permeability, ten additional rats were randomized into two groups: 1) CPR+Evans Blue (EB); 2) Sham+EB. Ventricular fibrillation was induced and untreated for 8 min, followed by 8 min of CPR, and resuscitation was attempted by defibrillation. Cerebral microcirculation was visualized at baseline, 2, 4 and 6 h after return of spontaneous circulation (ROSC). Brain edema was assessed by comparing wet-to-dry weight ratios after 6 h. S-100ß, NSE and EB concentrations were analyzed to determine BBB permeability damage. For results, Post-resuscitation cerebral microcirculation was impaired compared to baseline and sham control (p < 0.05). However, dysfunction was reduced in animals treated with PEG-20k compared to control (p < 0.05). Post-resuscitation cerebral edema as measured by wet-to-dry weight ratio was lower in PEG-20k compared to control (3.23 ±â€¯0.5 vs. 3.36 ±â€¯0.4, p < 0.05). CA and CPR increased BBB permeability and damaged neuronal cell with associated elevation of S-100ß sand NSE serum levels. PEG-20k administered during CPR improved cerebral microcirculation and reducing brain edema and injury.

Can Cranberry Juice Protect against Rotenone-Induced Toxicity in Rats?

The high polyphenols content of cranberry accounts for its strong antioxidant activity underlying the beneficial health effects of this fruit. Rotenone (ROT) is a specific inhibitor of mitochondrial complex I in the brain which leads to the generation of oxidative stress. To date, there are few data indicating that toxicity of ROT is not limited to the brain but can also affect other tissues. We aimed to examine whether ROT-induced oxidative stress could be counteracted by cranberry juice not only in the brain but also in the liver and kidney. Wistar rats were given the combined treatment with ROT and cranberry juice (CJ) for 35 days. Parameters of antioxidant status were determined in the organs. ROT enhanced lipid peroxidation solely in the brain. The increase in the DNA damage was noticed in all organs examined and in leukocytes. The beneficial effect of CJ on these parameters appeared only in the brain. Additionally, CJ decreased the activity of serum hepatic enzymes. The effect of CJ on antioxidant enzymes was not consistent, however, in some organs, CJ reversed changes evoked by ROT. Summing up, ROT can cause oxidative damage not only in the brain but also in other organs. CJ demonstrated a protective effect against ROT-induced toxicity.

Slack K+ channels attenuate NMDA-induced excitotoxic brain damage and neuronal cell death.

The neuronal Na+ -activated K+ channel Slack (aka Slo2.2, KNa 1.1, or Kcnt1) has been implicated in setting and maintaining the resting membrane potential and defining excitability and firing patterns, as well as in the generation of the slow afterhyperpolarization following bursts of action potentials. Slack activity increases significantly under conditions of high intracellular Na+ levels, suggesting this channel may exert important pathophysiological functions. To address these putative roles, we studied whether Slack K+ channels contribute to pathological changes and excitotoxic cell death caused by glutamatergic overstimulation of Ca2+ - and Na+ -permeable N-methyl-D-aspartic acid receptors (NMDAR). Slack-deficient (Slack KO) and wild-type (WT) mice were subjected to intrastriatal microinjections of the NMDAR agonist NMDA. NMDA-induced brain lesions were significantly increased in Slack KO vs WT mice, suggesting that the lack of Slack renders neurons particularly susceptible to excitotoxicity. Accordingly, excessive neuronal cell death was seen in Slack-deficient primary cerebellar granule cell (CGC) cultures exposed to glutamate and NMDA. Differences in neuronal survival between WT and Slack KO CGCs were largely abolished by the NMDAR antagonist MK-801, but not by NBQX, a potent and highly selective competitive antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type ionotropic glutamate receptors. Interestingly, NMDAR-evoked Ca2+ signals did not differ with regard to Slack genotype in CGCs. However, real-time monitoring of K+ following NMDAR activation revealed a significant contribution of this channel to the intracellular drop in K+ . Finally, TrkB and TrkC neurotrophin receptor transcript levels were elevated in NMDA-exposed Slack-proficient CGCs, suggesting a mechanism by which this K+ channel contributes to the activation of the extracellular-signal-regulated kinase (Erk) pathway and thereby to neuroprotection. Combined, our findings suggest that Slack-dependent K+ signals oppose the NMDAR-mediated excitotoxic neuronal injury by promoting pro-survival signaling via the BDNF/TrkB and Erk axis.

Short-Term High-Intensity Treadmill Exercise Promotes Ceramide-Dependent Extracellular Vesicle Secretion in the Central Nervous System of Mice.

BACKGROUND A lack of physical exercise, a critical aspect of a healthy lifestyle, contributes to several cerebral diseases, such as cognitive impairment, Parkinson disease (PD), and Alzheimer disease (AD). The purpose of the present study was to evaluate the effect of physical exercise on cerebral disease via released extracellular vesicles (EVs). MATERIAL AND METHODS Short-term high-intensity treadmill exercise was applied to assess the effect of physical activity on EVs in the serum and brain tissue. Immunofluorescence staining and western blot analysis were used to analyze biomarkers of EVs, including TSG101, HSC70, and CD63. Nanoparticle tracking analysis (NTA) was used to analyze the size and concentration of EVs. RESULTS Short-term high-intensity exercise increased the number of neuronal EVs in the brain. In the peripheral blood serum, the level of HSC70 showed a temporary increase after exercise and quickly returned to the normal level, whereas the levels of CD63 and TSG101 showed no obvious change in response to physical exercise. In brain tissue, the levels of HSC70 and TSG101 increased dramatically after exercise, while the level of CD63 remained unchanged. The concentration of EVs was significantly increased after exercise, while the mean diameter of the EVs showed no significant change. The levels of ceramide were significantly increased after exercise, and quickly returned to normal levels. CONCLUSIONS These data suggest that the secretion of EVs in the brain and blood is a transitory response to physical exercise and is dependent on ceramide synthesis.

Concerted outcome of metformin and low dose of radiation in modulation of cisplatin induced uremic encephalopathy via renal and neural preservation.

AIM: The therapeutic expediency of cisplatin was limited due to its nephrotoxic side effects, so this study planned to assess the nephrotic and neuroprotective impact of metformin (MET) and low-dose radiation (LDR) in cisplatin-prompted kidney injury and uremic encephalopathy (UE). METHODS: The effect of the 10-day MET treatment (200 mg/kg, orally) and/or fractionated LDR (0.25 Gy, of the total dose of 0.5 Gy, 1st and 7th day, respectively) on (5 mg/kg, intraperitoneally) cisplatin as a single dose was administered at the 5th day. Serum urea, creatinine and renal kidney injury molecule-1 were measured for the assessment of kidney function. Furthermore, the antioxidant potential in the renal and brain tissues was evaluated through, malondialdehyde and reduced glutathione estimation. Moreover, renal apoptotic markers: AMP-activated protein kinase, lipocalin, B-cell lymphoma 2 associated X protein, B-cell lymphoma 2, P53 and beclin 1 were estimated. UE was evaluated through the determination of serum inflammatory markers: nuclear factor kappa B, tumor-necrosis factor-α and interleukin 1 beta likewise, the cognitive deficits were assessed via forced swimming test, gamma-aminobutyric acid, n-methyl-d-aspartate and neuronal nitric oxide synthases besides AMP-activated protein kinase, light chain 3 and caspase3 levels in rats' cerebella. KEY FINDINGS: The obtained results revealed a noticeable improvement in the previously mentioned biochemical factors and behavioral tasks that was reinforced by histopathological examination when using the present remedy. SIGNIFICANCE: metformin and low doses of radiation afforded renoprotection and neuroprotection against cisplatin-induced acute uremic encephalopathy.

Hyperbaric oxygen therapy mobilized circulating stem cells and improved delayed encephalopathy after acute carbon monoxide poisoning with up-regulation of brain-derived neurotrophic factor.

Background Delayed encephalopathy (DE) is the most severe complication after acute carbon monoxide (CO) poisoning, which seriously affects the outcome of patients and leads to a high disability rate. Prior studies have shown that hyperbaric oxygen (HBO2) therapy is therapeutic for DE due to reducing immune-mediated neuropathology and thus improving cognitive performance. Methods In our present perspective study, five DE patients were treated regularly with HBO2 therapy. The mini-mental state examination (MMSE) and Barthel index (BI) were intermittently collected during their hospitalization for mental and physical status evaluation, the peripheral bloods were serially sampled to determine the concentration changes of circulating stem cells, as well as corresponding BDNF and neural markers. Results MMSE and BI showed series of improvements after multiple HBO2 therapies. The CD34+/CD90+ and CD34+/CD133+ dual positive cells, which were categorized as circulating stem cells, were observed an overall up-regulation since the beginning of the DE onset upon the application of HBO2 therapy. Characteristic neurotrophin BDNF, neural markers such as nestin and synaptophysin (SYP) were also up-regulated after exposure of HBO2. Conclusion The application of HBO2 therapy is of significance in improving the cognition of DE patients, along with mobilized circulating stem cells. We primarily infer that the CD34+/CD90+ and CD34+/CD133+ cells were mobilized by HBO2 exposure and have played a positive role in cognition improvement on DE patients by up-regulation of BDNF, nestin and SYP. The altering amount of circulating stem cells mobilized in peripheral blood could be a potential marker on predicting the outcome of DE.

The Effects of Dexmedetomidine Post-Conditioning on Cardiac and Neurological Outcomes After Cardiac Arrest and Resuscitation in Swine.

INTRODUCTION: One of the main contents of post-resuscitation care is to alleviate cardiac and neurological damage in cardiac arrest (CA) victims. Recently, dexmedetomidine pre- and post-conditioning have been shown to both effectively protect the heart and brain against regional ischemia reperfusion injury. In this study, we investigated the effects of dexmedetomidine post-conditioning on cardiac and neurological outcomes after CA and resuscitation in swine. METHODS: A total of 28 male domestic swine were randomized into four groups: sham, cardiopulmonary resuscitation (CPR), low-dose dexmedetomidine post-conditioning (LDP), and high-dose dexmedetomidine post-conditioning (HDP). Sham animals underwent the surgical preparation only. The animal model was established by 8 min of CA and then 5 min of CPR. After the animal was successfully resuscitated, a loading dose of 0.25 µg/kg of dexmedetomidine was intravenously injected followed by continuous infusion of 0.25 µg/kg/h for 6 h in the LDP group, and meanwhile a double dose of dexmedetomidine was similarly administered in the HDP group. The same amount of saline was given in the other two groups. All the resuscitated animals were monitored for 6 h and then returned to their cages for an additional 18 h of observation. RESULTS: After resuscitation, significantly greater cardiac, neurological dysfunction, and injuries were observed in all animals experiencing CA and resuscitation when compared with the sham group. However, the severity of cardiac and neurological damage was significantly milder in the two dexmedetomidine-treated groups than in the CPR group. Dexmedetomidine post-conditioning also significantly decreased post-resuscitation tissue inflammation, oxidative stress, and cell apoptosis and necroptosis in the heart and brain when compared with the CPR group. In addition, these protective effects produced by dexmedetomidine post-conditioning were significantly greater in the HDP group than in the LDP group. CONCLUSIONS: Dexmedetomidine post-conditioning dose-dependently improved post-resuscitation cardiac and neurological outcomes through the inhibition of tissue inflammation, oxidative stress, and cell apoptosis and necroptosis.

Gestational high fat diet protects 3xTg offspring from memory impairments, synaptic dysfunction, and brain pathology.

Maternal history for sporadic Alzheimer's disease (AD) predisposes the offspring to the disease later in life. However, the mechanisms behind this phenomenon are still unknown. Lifestyle and nutrition can directly modulate susceptibility to AD. Herein we investigated whether gestational high fat diet influences the offspring susceptibility to AD later in life. Triple transgenic dams were administered high fat diet or regular chow throughout 3 weeks gestation. Offspring were fed regular chow throughout their life and tested for spatial learning and memory, brain amyloidosis, tau pathology, and synaptic function. Gestational high fat diet attenuated memory decline, synaptic dysfunction, amyloid-ß and tau neuropathology in the offspring by transcriptional regulation of BACE-1, CDK5, and tau gene expression via the upregulation of FOXP2 repressor. Gestational high fat diet protects offspring against the development of the AD phenotype. In utero dietary intervention could be implemented as preventative strategy against AD.

Precisión de las características definitorias del diagnóstico de enfermería termorregulación ineficaz en recién nacidos / Accuracy of the defining characteristics of the nursing diagnosis: Ineffective thermoregulation in newborns

OBJETIVO: Identificar las medidas de precisión de las características definitorias del diagnóstico de enfermería termorregulación ineficaz en los recién nacidos. MÉTODO: Estudio de precisión diagnóstica de diseño transversal realizado en unidades de maternidad de medio y alto riesgo, localizada en la ciudad de Fortaleza-CE. Se evaluaron 216 recién nacidos para la identificación de las características definitorias del diagnóstico en estudio. Las medidas de precisión de las características definitorias se obtuvieron a partir de un modelo de 2 clases latentes con efectos aleatorios para el cálculo de los valores de sensibilidad y especificidad. RESULTADOS: Las características de frecuencia respiratoria aumentada y piel caliente al tacto presentaron valores de sensibilidad más altos (99,9%) y de especificidades menores (79 y 75%) y las características fluctuaciones de la temperatura corporal por encima y por debajo de los parámetros normales e hipertensión fueron las de mayor especificidad (80,4%) y sensibilidad (100%), respectivamente. CONCLUSIÓN: La característica fluctuación de la temperatura corporal por encima y por debajo de los parámetros normales puede ser más adecuadas para confirmar la presencia del diagnóstico, por haber presentado un mayor valor de especificidad

OBJECTIVE: To identify the measures of accuracy for defining characteristics of the nursing diagnosis: Ineffective thermoregulation in newborns. METHOD: Diagnostic accuracy study with cross-sectional design performed in medium and high-risk maternity units, located in Fortaleza city/Brazil. A total of 216 newborns were evaluated to identify the defining characteristics of the diagnosis under study. The measures of accuracy for defining characteristics were obtained from a latent class model with random effects for the calculation of sensitivity and specificity values. RESULTS: The characteristics of increased respiratory rate and warm skin to the touch had higher sensitivity values (99.9%) and lower specificity (79 and 75%) and the characteristics of body temperature fluctuations above and below the normal parameters and hypertension had the highest specificity (80.4 and 100%, respectively). CONCLUSION: The characteristic fluctuation of the body temperature above and below the normal parameters may be better to confirm the diagnosis, having presented a higher specificity value

Catechol protects against iron-mediated oxidative brain injury by restoring antioxidative metabolic pathways; and modulation of purinergic and cholinergic enzymes activities.

OBJECTIVES: This study was aimed at investigating neuroprotective effect of catechol on redox imbalance, cholinergic dysfunctions, nucleotide hydrolysing enzymes activities, and dysregulated metabolic pathways in iron-mediated oxidative brain injury. METHODS: Oxidative injury was induced in brain tissues by incubating with 0.1 mm FeSO4 and treated with different concentrations of catechol. KEY FINDINGS: Catechol significantly elevated glutathione level, superoxide dismutase and catalase activities, while depleting malondialdehyde and nitric oxide levels. It also inhibited the activities of acetylcholinesterase, butyrylcholinesterase, and ATPase, with concomitant elevation of ENTPDase activity. GC-MS analysis revealed that treatment with catechol completely depleted oxidative-generated lipid metabolites. While LC-MS analysis revealed depletion of oxidative-generated metabolites in brain tissues treated with catechol, with concomitant restoration of oxidative-depleted metabolites. Catechol also led to reactivation of oxidative-inactivated taurine and hypotaurine, purine, glutathione, glycerophospholipid, nicotinate and nicotinamide, fructose and mannose, pyrimidine metabolisms and pentose phosphate pathways. Catechol was predicted in silico to be permeable across the blood-brain barrier with a predicted oral LD50 value of 100 mg/kg and a toxicity class of 3. CONCLUSION: These results suggest the neuroprotective effects of catechol in iron-mediated oxidative brain injury.

The Importance of Marine Omega-3s for Brain Development and the Prevention and Treatment of Behavior, Mood, and Other Brain Disorders.

Most of the global population is deficient in long-chain marine omega-3s. In particular, docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, is important for brain and eye development. Additionally, DHA plays a significant role in mental health throughout early childhood and even into adulthood. In the brain, DHA is important for cellular membrane fluidity, function and neurotransmitter release. Evidence indicates that a low intake of marine omega-3s increases the risk for numerous mental health issues, including Attention Deficit Hyperactivity Disorder (ADHD), autism, bipolar disorder, depression and suicidal ideation. Studies giving supplemental marine omega-3s have shown promise for improving numerous mental health conditions. This paper will review the evidence surrounding marine omega-3s and mental health conditions.

Tratamiento hipolipemiante en la prevención secundaria de la enfermedad cerebrovascular isquémica / Lipid-lowering treatment in secondary prevention of ischaemic cerebrovascular disease

El accidente cerebrovascular es la segunda causa de mortalidad después del infarto de miocardio y la principal causa de discapacidad adquirida. Los pacientes con ictus isquémico tienen un elevado riesgo de posteriores episodios vasculares, incluyendo ictus recurrente, infarto de miocardio y muerte de causa vascular. Los primeros estudios epidemiológicos mostraron una relación débil o inexistente entre la colesterolemia y el ictus. Posteriormente, los estudios de intervención con estatinas revelaron una reducción del riesgo de recurrencia de episodios cerebrovasculares. El Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL), primer ensayo clínico diseñado para analizar los efectos de la terapia con estatinas en la prevención secundaria del ictus, demostró que el tratamiento con atorvastatina 80mg/día reducía la recurrencia de ictus en pacientes con un accidente cerebrovascular isquémico reciente establecido o transitorio, con un modesto aumento en la tasa de ictus hemorrágico. Estudios posteriores han recabado los beneficios de la terapia de estatinas, con ezetimiba o inhibidores de PCSK9 tanto en la prevención primaria como secundaria del accidente cerebrovascular isquémico. Dado que el 80% de los episodios cerebrovasculares recurrentes pueden prevenirse, hemos considerado de interés realizar una revisión narrativa de los beneficios de la terapia hipolipemiante en la prevención secundaria de la enfermedad cerebrovascular isquémica

Stroke is the second cause of death after myocardial infarction, and the main cause of acquired disability. Patients with ischaemic stroke have a higher risk of future vascular events, including recurrent stroke, myocardial infarction, and death by vascular cause. The initial epidemiological studies demonstrated a weak or non-existent relationship between cholesterolaemia and stroke. Subsequently, statin intervention trials showed a reduction in the risk of recurrence of cerebrovascular events. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL), the first clinical trial designed to assess effects of statin therapy in secondary stroke prevention, highlighted the reduction of stroke recurrence with atorvastatin 80mg/daily in patients with a recent ischaemic established or transient stroke, with a modest increase in the rate of haemorrhagic stroke. Successive studies have also reported the benefits of statin therapy combined with ezetimibe or PCSK9 inhibitors in primary and secondary ischaemic stroke prevention. Since 80% of recurrent cerebrovascular events could be prevented, it is considered of interest to carry out a narrative review of the benefits of lipid-lowering therapy in the secondary prevention of ischaemic cerebrovascular disease