Stroke is a major health problem world-wide and its burden has been rising in last few decades. Until now tissue plasminogen activator is only approved treatment for stroke. Angiogenesis plays a ...vital role for striatal neurogenesis after stroke. Administration of various growth factors in an early post ischemic phase, stimulate both angiogenesis and neurogenesis and lead to improved functional recovery after stroke. However vascular endothelial growth factors (VEGF) is the most potent angiogenic factor for neurovascularization and neurogenesis in ischemic injury can be modulated in different ways and thus can be used as therapy in stroke. In response to the ischemic injury VEGF is released by endothelial cells through natural mechanism and leads to angiogenesis and vascularization. This release can also be up regulated by exogenous administration of Mesenchymal stem cells, by various physical therapy regimes and electroacupuncture, which further potentiate the efficacy of VEGF as therapy in post stroke recovery. Recent published literature was searched using PubMed and Google for the article reporting on methods of up regulation of VEGF and therapeutic potential of growth factors in stroke.
The loss of function mutations (biallelic) in frataxin (FXN) has primarily been implicated in Friedreich's ataxia (FRDA), an autosomal recessive cerebellar ataxia. The protein product of FXN is a ...nuclear-encoded mitochondrial protein required for the biogenesis of iron- clusters (Fe-S). FRDA is characterized by neurological and non-neurological features which show variable expression in affected individuals. An inverse relationship has been demonstrated between GAA repeat size and age at onset and explains 50% variability of the age at onset. MtDNA variations and haplogroups could be one of the contributory factors to explain the remaining heterogeneity in FRDA, since mitochondrial oxidative stress is thought to be involved in the pathogenesis of FRDA.
In our study, targeted resequencing of the D-loop and coding region of mitochondrial genes (ND1-6 and ATP) was conducted in 30 genetically confirmed FRDA patients and 62 ethnicity-matched unrelated healthy controls to identify the functionally important mtDNA variations and to trace the mitochondrial lineage of Indian FRDA patients. Cumulative mitochondrial SNP scores were computed for the identified variations in the functional region and haplogroups were determined by Haplogrep.
A significantly higher load of overall mitochondrial variations (with a trend toward the coding region) per individual was noted among FRDA cases rather than controls (p-value<0.03). A non-synonymous variation (p. L237M) in ND2 was over-represented among FRDA cases (p-value 0.04). This variation has a reported association with longevity and myocardial infarction. We also observed over-representation of H haplogroup (Caucasian mitochondrial haplogroup) among FRDA patients. We have not observed the influence of mitochondrial variations and haplogroup upon age at onset of FRDA.
Overall, our study identifies the functionally important variations and mitochondrial lineage of Indian FRDA cases and, that underscores the importance of studying the role of mitochondrial genome variations in FRDA.
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