Peripheral nerve injury is a complex condition with a variety of signs and symptoms such as numbness, tingling, jabbing, throbbing, burning or sharp pain. Peripheral nerves are fragile in nature and can easily get damaged due to acute compression or trauma which may lead to the sensory and motor functions deficits and even lifelong disability. After lesion, the neuronal cell body becomes disconnected from the axon's distal portion to the injury site leading to the axonal degeneration and dismantlement of neuromuscular junctions of targeted muscles. In spite of extensive research on this aspect, complete functional recovery still remains a challenge to be resolved. This review highlights detailed pathophysiological events after an injury to a peripheral nerve and the associated factors that can either hinder or promote the regenerative machinery. In addition, it throws light on the available therapeutic strategies including supporting therapies, surgical and non-surgical interventions to ameliorate the axonal regeneration, neuronal survival, and reinnervation of peripheral targets. Despite the availability of various treatment options, we are still lacking the optimal treatments for a perfect and complete functional regain. The need for the present age is to discover or design such potent compounds that would be able to execute the complete functional retrieval. In this regard, plant-derived compounds are getting more attention and several recent reports validate their remedial effects. A plethora of plants and plant-derived phytochemicals have been suggested with curative effects against a number of diseases in general and neuronal injury in particular. They can be a ray of hope for the suffering individuals.

Brain is a vital organ of the human body which performs very important functions such as analysis, processing, coordination, and execution of electrical signals. For this purpose, it depends on a complex network of nerves which are ensheathed in lipids tailored myelin; an abundant source of lipids in the body. The nervous system is enriched with important classes of lipids; sphingolipids and cholesterol which compose the major portion of the brain particularly in the form of myelin. Both cholesterol and sphingolipids are embedded in the microdomains of membrane rafts and are functional units of the neuronal cell membrane. These molecules serve as the signaling molecules; hold important roles in the neuronal differentiation, synaptogenesis, and many others. Thus, their adequate provision and active metabolism are of crucial importance in the maintenance of physiological functions of brain and body of an individual. In the present review, we have highlighted the physiological roles of cholesterol and sphingolipids in the development of the nervous system as well as the association of their altered metabolism to neurological and neurodegenerative diseases.

Consanguineous Pakistani pedigrees segregating deafness have contributed decisively to the discovery of 31 of the 68 genes associated with nonsyndromic autosomal recessive hearing loss (HL) worldwide. In this study, we utilized genome-wide genotyping, Sanger and exome sequencing to identify 163 DNA variants in 41 previously reported HL genes segregating in 321 Pakistani families. Of these, 71 (43.6%) variants identified in 29 genes are novel. As expected from genetic studies of disorders segregating in consanguineous families, the majority of affected individuals (94.4%) are homozygous for HL-associated variants, with the other variants being compound heterozygotes. The five most common HL genes in the Pakistani population are SLC26A4, MYO7A, GJB2, CIB2 and HGF, respectively. Our study provides a profile of the genetic etiology of HL in Pakistani families, which will allow for the development of more efficient genetic diagnostic tools, aid in accurate genetic counseling and guide application of future gene-based therapies. These findings are also valuable in interpreting pathogenicity of variants that are potentially associated with HL in individuals of all ancestries. The Pakistani population, and its infrastructure for studying human genetics, will continue to be valuable to gene discovery for HL and other inherited disorders.

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