Stromal cell-derived factor-1is a chemoattractant produced by bone marrow stromal cell lines. It is recognized as a critical factor in the immune and central nervous systems as well as exerting a role in cancer. SDF-1 activates two G protein-coupled receptors, CXCR4 and CXCR7; these are expressed in both the developing and mature central nervous systems and participate in multiple physiological and pathological events, e.g. inflammatory response, neurogenesis, angiogenesis, hematopoiesis, cancer metastasis, and HIV infection. After an ischemic stroke, SDF-1 levels robustly increase in the penumbra regions and participate in adult neural functional repair. Here we will review recent findings related to SDF-1 and its receptor, analyze their functions in neurogenesis after brain ischemic injury: i.e. how the system promotes the proliferation, differentiation and migration of neural precursor cells and mediates axonal elongation and branching.

Background and Purpose—: Constraint-induced movement therapy (CIMT) improves functional outcome in patients with stroke possibly through structural plasticity. We hypothesized that CIMT could enhance axonal growth by overcoming the intrinsic growth–inhibitory signals, leading eventually to improved behavioral performance in stroke rats. Methods—: Focal cerebral ischemia was induced by intracerebral injection of endothelin-1. Adult Wistar rats were divided into a sham-operated group, an ischemic group, and an ischemic group treated with CIMT. CIMT started at postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine was injected into the contralateral sensorimotor cortex at postoperative day 14 to trace crossing axons at the cervical spinal cord. The expressions of Nogo-A, Nogo receptor, RhoA, and Rho-associated kinase in the peri-infarct cortex, and the expressions of biotinylated dextran amine, growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated spinal cord were measured by immunohistochemistry and Western blots. Behavioral recovery was analyzed at postoperative days 29 to 32. Results—: Infarct volumes were not different between groups after stroke. CIMT significantly increased the length and the number of midline crossings of contralateral corticospinal axons to the denervated cervical spinal cord. CIMT significantly decreased the expressions of Nogo-A/Nogo receptor and RhoA/Rho-associated kinase in the peri-infarct cortex, and increased the expressions of growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated cervical spinal cord. Behavioral performances assessed by the beam-walking test and the water maze test were improved significantly by CIMT. Conclusions—: CIMT promoted poststroke synaptic plasticity and axonal growth at least partially by overcoming the intrinsic growth–inhibitory signaling, leading to improved behavioral outcome.

Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of the PARP superfamily, with its primary function being the facilitation of DNA damage repair processes. Parthanatos is a type of regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including the accumulation of ADP-ribose polymers (PAR), binding of PAR and apoptosis-inducing factor (AIF), release of AIF from the mitochondria, the translocation of the AIF/macrophage migration inhibitory factor (MIF) complex, and massive MIF-mediated DNA fragmentation. Over the past few decades, the role of PARP-1 in central nervous system health and disease has received increasing attention. In this review, we discuss the biological functions of PARP-1 in neural cell proliferation and differentiation, memory formation, brain ageing, and epigenetic regulation. We then elaborate on the involvement of PARP-1 and PARP-1-dependant parthanatos in various neuropathological processes, such as oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, autophagy damage, and endoplasmic reticulum (ER) stress. Additional highlight contains PARP-1's implications in the initiation, progression, and therapeutic opportunities for different neurological illnesses, including neurodegenerative diseases, stroke, autism spectrum disorder (ASD), multiple sclerosis (MS), epilepsy, and neuropathic pain (NP). Finally, emerging insights into the repurposing of PARP inhibitors for the management of neurological diseases are provided. This review aims to summarize the exciting advancements in the critical role of PARP-1 in neurological disorders, which may open new avenues for therapeutic options targeting PARP-1 or parthanatos.

Objective: To assess the association between low-density lipoprotein cholesterol (LDL-c) and risk of Alzheimer's disease (AD). Methods: Embase, Pubmed, and Web of Science were searched until June 2019. Standard mean difference (SMD) with 95% confidence intervals (CI) was estimated using random-effects models. Results: Our meta-analysis of 26 studies revealed higher levels of LDL-c in AD than that of non-dementia controls (SMD = 0.35, 95% CI 0.12–0.58, p < 0.01). The meta-regression analysis on confounders showed that age (p < 0.01, Adj R-squared = 92.41%) and cardiovascular disease (p = 0.01, Adj R-squared = 85.21%), but not the body mass index, education, smoking, hypertension and diabetes mellitus, exerted an impact on the relationship between LDL-c and risk of ICH. Further subgroup analysis of age showed LDL-c levels in AD patients aged 60–70 were higher than that of non-dementia (60 ≤ age < 70: SMD = 0.80, 95% CI 0.23–1.37, p < 0.01); but no association between the SMD of AD in LDL-c and age over 70 was noted across the studies (70 ≤ age < 77: SMD = −0.02, 95% CI −0.39~0.34, p = 9.0; 77 ≤ age < 80: SMD = 0.15, 95% CI −0.17~0.47, p = 0.35; ≥80: SMD = 0.53, 95% CI −0.04~1.11, p = 0.07). The concentrations of LDL-c during the quintile interval of 3~4 were positively associated with AD (121 ≤ concentration < 137: SMD = 0.98, 95% CI 0.13~1.82, p = 0.02; ≥137: SMD = 0.62, 95% CI 0.18~1.06, p < 0.01); whereas there was no correlation between AD and LDL-c within the quintile interval of 1~2 (103.9 ≤ concentration < 112: SMD = 0.08, 95% CI −0.20~0.35, p = 0.59; 112 ≤ concentration < 121: SMD = −0.26, 95% CI −0.58~0.06, p = 0.11). Conclusions: Elevated concentration of LDL-c (>121 mg/dl) may be a potential risk factor for AD. This association is strong in patients aged 60–70 years, but vanishes with advancing age.

Intracerebral hemorrhage (ICH) has the highest mortality rate in all strokes. However, controversy still exists concerning the association between plasma homocysteine (Hcy) and ICH. A systematic review and meta-analysis was conducted using Pubmed, Embase, and Web of Science up to April 18, 2017. Standard mean difference (SMD) for mean differences of plasma Hcy levels with 95% confidence intervals (CI) was calculated. Seven studies including 667 ICH patients and 1821 ischemic stroke patients were identified for meta-analysis. Our results showed that Hcy levels in ICH patients were significantly higher than those in healthy controls (SMD = 0.59, 95% CI = 0.51–0.68, P < 0.001); no statistic differences were found in the comparisons of Hcy levels between ICH and ischemic stroke (SMD = −0.03, 95% CI = −0.13–0.06, P > 0.05); further subgroup analysis of ethnicity (Asians: SMD = 0.57, 95% CI = 0.48–0.66, P < 0.001; Caucasians: SMD = 0.77, 95% CI = 0.51–1.02, P < 0.001) and sample size (small samples: SMD = 0.55, 95% CI = 0.30–0.80, P < 0.001; large samples size: SMD = 0.60, 95% CI = 0.51–0.69, P < 0.001) in relation to Hcy levels between ICH and healthy controls did not change these results. In conclusion, Hcy level may be an aggravating factor in atherosclerosis, which is positively associated with high risk of ICH. Race-specific differences between Asians and Caucasians have no impact on the risk of ICH.

Constraint-induced movement therapy (CIMT) has been extensively used for stroke rehabilitation. CIMT encourages use of the impaired limb along with restraint of the ipsilesional limb in daily life, and may promote behavioral recovery and induce structural changes in brain after stroke. The aim of this study was to investigate whether CIMT enhances neurogenesis in rat brain after stroke that was generated by middle cerebral artery occlusion. Adult rats were divided into sham group, ischemia group and ischemia treated with CIMT group. Rats of CIMT group were treated with a plaster cast to restrain the healthy forelimb for 14 days beginning 1 week after ischemia. The proliferation of neuronal cells labeled with bromodeoxyuridine (BrdU) and behavioral recovery were analyzed at day 29 after ischemia. We also measured the tissue level of stromal cell-derived factor 1 (SDF-1) by ELISA. SDF-1 might be involved in the regulation of neurogenesis following stroke. In the subventricular zone of the animals treated with CIMT, there was a significant increase in the number of BrdU-positive cells (135 ± 18, P < 0.05), compared with ischemia group (87 ± 12) or sham group (18 ± 3.6). Likewise, in the dentate gyrus, animals treated with CIMT showed a significant increase in BrdU-positive cells (296 ± 26, P < 0.05) compared with ischemia group (225 ± 18) or sham group (162 ± 11). CIMT treatment after stroke significantly improved behavioral performances and increased the SDF-1 protein levels in the cortex and dentate gyrus. In conclusion, CIMT treatment enhances neurogenesis and functional recovery after stroke.