leptin and Cerebral-Infarction

This study was to investigate the effect of proprioceptive neuromuscular facilitation techniques (NFT) on osteoporosis and serum leptin level in cerebral infarction patients or rats.. Forty cerebral infarction rats were randomly grouped into control, sham operation, conventional treatment (CT) group and CT+NFT group. Fifty-two stroke patients with hemiplegia were included in this study.. The bone mineral densities (BMD) of proximal hemiplegia limbs and serum ALP, BALP, BGP, IL-6 and leptin levels were detected using commercial kits.. In cerebral infarction rats, the BMD, BGP, BALP, ALP and leptin concentrations in the CT+NFT group was higher compared with the control and CT group, while serum IL-6 level was more reduced by CT+NFT than control and CT. In cerebral infarction patients, both CT and CT+NFT increased the BMD, ALP, BGP and leptin levels. In addition, compared with CT, the BMD, ALP, BGP and leptin levels were markedly increased by CT+NFT. C Conclusion: NFC elevated the BMD of hemiplegia limbs, serum ALP, BGP, IL-6 and leptin levels and, thus, alleviated osteoporosis in rats and patients with cerebral infarction.

Topics: Aged; Analysis of Variance; Animals; Bone Density; Cerebral Infarction; Disease Models, Animal; Female; Follow-Up Studies; Hemiplegia; Humans; Leptin; Magnetic Resonance Imaging; Male; Middle Aged; Muscle Stretching Exercises; Osteoporosis; Rats; Tomography Scanners, X-Ray Computed

The purpose of this study was to evaluate the neuroprotective effect of leptin on a non-human primate model of cerebral ischemia. A total of 39 Guangxi macaques were used to establish the primate cerebral-ischemia model. HE staining was used to evaluated the pathological changes. Moreover, magnetic resonance imaging was used for the detection of embolic area. The measurements of behavior observation and cerebral infarction area were also performed. They all received autologous thrombus operation. Furthermore, western blot and RT-PCR were also used to detect the protein and mRNA expression levels of apoptosis-related factors. Our results showed that leptin could reduce the volume of cerebral infarction by about 35%. Behavioral defects can be significantly improved. In addition, mid-term and long-term behavioral deficiencies had been significantly improved by leptin. Moreover, leptin significantly decreased the expression levels of caspase-3 and Bax, and increased the expression levels of Bcl-2. In conclusion, leptin has neuroprotective effects on cerebral ischemia by effectively reducing the volume of cerebral infarction.

Topics: Animals; Apoptosis; Brain; Brain Ischemia; Caspase 3; Cerebral Infarction; China; Leptin; Neuroprotective Agents; Primates

Aneurysmal subarachnoid hemorrhage (SAH) is associated with a high mortality rate and may leave surviving patients severely disabled. After the initial hemorrhage, clinical outcome is further compromised by the occurrence of delayed cerebral ischemia (DCI). Overweight and obesity have previously been associated with protective effects in the post-bleeding phase. The aim of this study was to assess the effects of a patient's body mass index (BMI) and leptin levels on the occurrence of DCI, DCI-related cerebral infarction, and clinical outcome. In total, 263 SAH patients were included of which leptin levels were assessed in 24 cases. BMI was recorded along disease severity documented by the Hunt and Hess and modified Fisher scales. The occurrence of clinical or functional DCI (neuromonitoring, CT Perfusion) was assessed. Long-term clinical outcome was documented after 12 months (extended Glasgow outcome scale). A total of 136 (51.7%) patients developed DCI of which 72 (27.4%) developed DCI-related cerebral infarctions. No association between BMI and DCI occurrence (P = .410) or better clinical outcome (P = .643) was identified. Early leptin concentration in serum (P = .258) and CSF (P = .159) showed no predictive value in identifying patients at risk of unfavorable outcomes. However, a significant increase of leptin levels in CSF occurred from 326.0 pg/ml IQR 171.9 prior to DCI development to 579.2 pg/ml IQR 211.9 during ongoing DCI (P = .049). In our data, no association between obesity and clinical outcome was detected. After DCI development, leptin levels in CSF increased either by an upsurge of active transport or disruption of the blood-CSF barrier. This trial has been registered at ClinicalTrials.gov (NCT02142166) as part of a larger-scale prospective data collection. BioSAB: https://clinicaltrials.gov/ct2/show/NCT02142166.

Topics: Body Mass Index; Brain Ischemia; Cerebral Infarction; Humans; Leptin; Subarachnoid Hemorrhage

Recent research has indicates that leptin plays a protective role in traumatic brain injury. We studied the protective effect of leptin on cerebral ischemia/reperfusion injury by using mice transient focal cerebral ischemia/reperfusion injury model.. The distribution of 125I-leptin in the mouse brain was assessed by radioimmunoassay method. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for two hours followed by 24 hours reperfusion. The neurologic deficits and infarct volume were determined using the Longa's score and 2,3,5-triphenyltetrazolium chloride staining, respectively. Regional cerebral blood flow was monitored by a laser-Doppler blood flowmeter. The levels of malondialdehyde, nitric oxide, nitric oxide synthase, and superoxide dismutase were detected according to respective assay kit. The histologic changes and neuronal apoptosis were observed with hematoxylin and eosin and transferase-mediated dUTP-biotin nick end labeling staining, respectively. The expression of B-cell lymphoma/leukemia-2 (Bcl-2) and cysteineasparateprotease-3 (caspase-3) were investigated by Western blot and real-time polymerase chain reaction assay.. Leptin decreased infarct volume and neurologic defects and improved regional cerebral blood flow and microvascular branch blood flow after injury. The malondialdehyde and nitric oxide levels were reduced, and superoxide dismutase level was increased after leptin treatment, which also minimized histologic changes and neuronal apoptosis, led to the upregulation of Bcl-2 and downregulation of caspase-3 expression after injury.. Peripherally administered leptin crossed the blood-brain barrier and was distributed into multiple regions of the brain; in the brain, leptin directly alleviated the injury-evoked damages by reducing oxidative stress and neuronal apoptosis.

Topics: Animals; Apoptosis; Brain Chemistry; Brain Ischemia; Cerebral Infarction; Cerebrovascular Circulation; Disease Models, Animal; Leptin; Male; Malondialdehyde; Mice; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Superoxide Dismutase

Leptin is an adipose hormone endowed with angiopoietic, neurotrophic, and neuroprotective properties. We tested the hypothesis that leptin might act as an endogenous mediator of recovery after ischemic stroke and investigated whether nuclear transcription factors kappaB activation is involved in leptin-mediated neuroprotection.. The antiapoptotic effects of leptin were evaluated in cultured mouse cortical neurons from wild-type or NF-kappaB/c-Rel(-/-) mice exposed to oxygen-glucose deprivation. Wild-type, c-Rel(-/-) and leptin-deficient ob/ob mice were subjected to permanent middle cerebral artery occlusion. Leptin production was measured in brains from wild-type mice with quantitative reverse transcriptase-polymerase chain reaction and immunostaining. Mice received a leptin bolus (20 microg/g) intraperitoneally at the onset of ischemia.. Leptin treatment activated the nuclear translocation of nuclear transcription factors kappaB dimers containing the c-Rel subunit, induced the expression of the antiapoptotic c-Rel target gene Bcl-xL in both control and oxygen-glucose deprivation conditions, and counteracted the oxygen-glucose deprivation-mediated apoptotic death of cultured cortical neurons. Leptin-mediated Bcl-xL induction and neuroprotection against oxygen-glucose deprivation were hampered in cortical neurons from c-Rel(-/-) mice. Leptin mRNA was induced and the protein was detectable in microglia/macrophage cells from the ischemic penumbra of wild-type mice subjected to permanent middle cerebral artery occlusion. Ob/ob mice were more susceptible than wild-type mice to the permanent middle cerebral artery occlusion injury. Leptin injection significantly reduced the permanent middle cerebral artery occlusion-mediated cortical damage in wild-type and ob/ob mice, but not in c-Rel(-/-) mice.. Leptin acts as an endogenous mediator of neuroprotection during cerebral ischemia. Exogenous leptin administration protects against ischemic neuronal injury in vitro and in vivo in a c-Rel-dependent manner.

Topics: Animals; bcl-X Protein; Blotting, Western; Brain Ischemia; Cells, Cultured; Cerebral Cortex; Cerebral Infarction; DNA; Female; Fluorescent Antibody Technique; Glucose; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hypoxia; Immunohistochemistry; Immunoprecipitation; Leptin; Mice; Mice, Inbred C57BL; NF-kappa B; Pregnancy; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Up-Regulation

Depression is a frequent mood disorder that affects around 33% of stroke patients and has been associated with both poorer outcome and increased mortality. Our aim was to test the possible association between inflammatory and neurotrophic molecular markers and the development of post-stroke depression.. We studied 134 patients with a first episode of ischemic stroke without previous history of depression or speech disorders. We screened for the existence of major depression symptoms in accordance with DSM-IV criteria and a Yesavage Geriatric Depression Scale (GDS) score >11 at discharge and 1 month after stroke. At these times, serum levels of molecular markers of inflammation [interleukin (IL)-1beta, IL-6, intracellular adhesion molecule 1 (ICAM-1), tumor necrosis factor (TNF)-alpha, leptin and high-sensitivity C-reactive protein (hs-CRP)] and neurotrophic factors [brain-derived neurotrophic factor (BDNF)] were measured by enzyme-linked immunosorbent assay (ELISA).. Twenty-five patients (18.7%) were diagnosed as having major depression at discharge. Out of 104 patients who completed the follow-up period, 23 were depressed at 1 month (22.1%). Patients with major depression showed higher serum leptin levels at discharge [43.4 (23.4-60.2) v. 6.4 (3.7-16.8) ng/ml, p<0.001] and at 1 month after stroke [46.2 (34.0-117.7) v. 6.4 (3.4-12.2) ng/ml, p<0.001). Serum levels of leptin >20.7 ng/ml were independently associated with post-stroke depression [odds ratio (OR) 16.4, 95% confidence interval (CI) 5.2-51.5, p<0.0001]. Leptin levels were even higher in the eight patients who developed depression after discharge [114.6 (87.6-120.2) v. 7.2 (3.6-13.6) ng/ml, p<0.0001].. Serum leptin levels at discharge are found to be associated with post-stroke depression and may predict its development during the next month.

Topics: Aged; Aged, 80 and over; Biomarkers; Cerebral Infarction; Depressive Disorder, Major; Female; Follow-Up Studies; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Odds Ratio; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors; Statistics as Topic; Tomography, X-Ray Computed

Although epidemiological studies reveal an increased incidence of obesity and an association between obesity and the prevalence/severity of ischemic stroke, little is known about the mechanisms that link obesity to ischemic stroke. This study tested the hypothesis that obesity exacerbates the cerebrovascular dysfunction and tissue injury induced by brain ischemia and reperfusion.. The adhesion of leukocytes and platelets in cerebral venules, blood-brain barrier permeability, brain water content, and infarct volume were measured in wild-type, obese (ob/ob), and leptin-reconstituted ob/ob mice subjected to 30 minutes middle cerebral artery occlusion and reperfusion. Tissue and plasma cytokine levels were determined by cytometric bead array, and a role for monocyte chemoattractant protein-1 and interleukin-6 was assessed using blocking antibodies.. Compared with wild-type mice, ob/ob exhibited larger increases in leukocyte and platelet adhesion, blood-brain barrier permeability, water content, and infarct volume after middle cerebral artery occlusion-reperfusion. Reconstitution of leptin in ob/ob mice tended to further enhance all reperfusion-induced responses. Ob/ob mice also exhibited higher plasma levels of monocyte chemoattractant protein-1 and interleukin-6 than wild-type mice. Immunoneutralization of monocyte chemoattractant protein-1, but not interleukin-6, reduced infarct volume in ob/ob mice.. Obesity worsens the inflammatory and injury responses to middle cerebral artery occlusion and reperfusion by a mechanism independent of leptin deficiency. monocyte chemoattractant protein-1 appears to contribute to the exaggerated responses to ischemic stroke in obese mice.

Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Capillary Permeability; Cell Adhesion; Cerebral Infarction; Cerebrovascular Circulation; Chemokine CCL2; Encephalitis; Infarction, Middle Cerebral Artery; Interleukin-6; Leptin; Leukocytes; Male; Mice; Mice, Obese; Obesity; Platelet Adhesiveness; Reperfusion Injury; Stroke