Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice.

The extracellular matrix fragment perlecan domain V is neuroprotective and functionally restorative following experimental stroke. As neurogenesis is an important component of chronic post-stroke repair, and previous studies have implicated perlecan in developmental neurogenesis, we hypothesized that domain V could have a broad therapeutic window by enhancing neurogenesis after stroke. We demonstrated that domain V is chronically increased in the brains of human stroke patients, suggesting that it is present during post-stroke neurogenic periods.

The potential role of perlecan domain V as novel therapy in vascular dementia.

Vascular dementia (VaD) is the second most common cause of dementia and leads to a decline in cognitive thinking via conditions that lead to blockage or reduced blood flow to the brain. It is a poorly understood disease, and the changes that occur are often linked to other types of dementia such as Alzheimer's disease. To date, there are no approved therapies or drugs to treat the symptoms of VaD, even though there is some evidence of drugs approved for Alzheimer's that might have some benefit in patients diagnosed with VaD.

Investigating the role of perlecan domain V in post-ischemic cerebral angiogenesis.

Cerebral angiogenesis is an important process for physiological events such as brain development, but it also occurs in pathological conditions such as stroke. Defined as the generation of new blood vessels from preexisting vasculature, angiogenesis after ischemic stroke is important to limit the subsequent neuronal injury and death, as well as contribute to neurorepair. However, current therapies for ischemic stroke are largely focused on reestablishing uninterrupted blood flow, an important but inherently risky proposition.

MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway.

Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells.

The α7-nicotinic acetylcholine receptor and MMP-2/-9 pathway mediate the proangiogenic effect of nicotine in human retinal endothelial cells.

Purpose: Nicotine, the active component of cigarette smoke, has been found to stimulate angiogenesis in several experimental systems. In this study, the Matrigel duplex assay (Matrigel; BD Biosciences, Franklin Lakes, NJ) and the rat retinal explant assay were used to explore the molecular mechanisms underlying the proangiogenic effects of nicotine in endothelial cells.

Methods: Western blot analysis was performed to determine the nicotinic acetylcholine receptor (nAChR) subtypes expressed on primary human retinal microvascular endothelial cells (HRMECs).

Thimerosal induces apoptosis in a neuroblastoma model via the cJun N-terminal kinase pathway.

The cJun N-terminal kinase (JNK)-signaling pathway is activated in response to a variety of stimuli, including environmental insults, and has been implicated in neuronal apoptosis. In this study, we investigated the role that the JNK pathway plays in neurotoxicity caused by thimerosal, an ethylmercury-containing preservative. SK-N-SH cells treated with thimerosal (0-10 microM) showed an increase in the phosphorylated (active) form of JNK and cJun with 5 and 10 microM thimerosal treatment at 2 and 4 h.