losartan-potassium and Cicatrix

Erythropoietin (EPO) has been recognized as a neuroprotective agent. In animal models of neonatal brain injury, exogenous EPO has been shown to reduce lesion size, improve structure and function. Experimental studies have focused on short course treatment after injury. Timing, dose and length of treatment in preterm brain damage remain to be defined. We have evaluated the effects of high dose and long-term EPO treatment in hypoxic-ischemic (HI) injury in 3 days old (P3) rat pups using histopathology, magnetic resonance imaging (MRI) and spectroscopy (MRS) as well as functional assessment with somatosensory-evoked potentials (SEP). After HI, rat pups were assessed by MRI for initial damage and were randomized to receive EPO or vehicle. At the end of treatment period (P25) the size of resulting cortical damage and white matter (WM) microstructure integrity were assessed by MRI and cortical metabolism by MRS. Whisker elicited SEP were recorded to evaluate somatosensory function. Brains were collected for neuropathological assessment. The EPO treated animals did not show significant decrease of the HI induced cortical loss at P25. WM microstructure measured by diffusion tensor imaging was improved and SEP response in the injured cortex was recovered in the EPO treated animals compared to vehicle treated animals. In addition, the metabolic profile was less altered in the EPO group. Long-term treatment with high dose EPO after HI injury in the very immature rat brain induced recovery of WM microstructure and connectivity as well as somatosensory cortical function despite no effects on volume of cortical damage. This indicates that long-term high-dose EPO induces recovery of structural and functional connectivity despite persisting gross anatomical cortical alteration resulting from HI.

Topics: Animals; Animals, Newborn; Astrocytes; Cerebral Cortex; Cicatrix; Diffusion Tensor Imaging; Disease Models, Animal; Erythropoietin; Evoked Potentials, Somatosensory; Female; Hypoxia-Ischemia, Brain; Intermediate Filaments; Male; Metabolome; Metabolomics; Myelin Sheath; Neurons; Neuroprotective Agents; Organ Size; Proton Magnetic Resonance Spectroscopy; Rats; Time Factors

EPO has been shown to have beneficial effects in a variety of CNS injury models. The purpose of this study was to evaluate the effects of EPO on nerve regeneration and functional recovery in a rat model of peripheral nerve surgery.. The sciatic nerve of the rat with a 10-mm defect was bridged with a silicone rubber tube. Forty adult male Sprague-Dawley rats were assigned to the control or experimental groups to receive an intraperitoneal injection of NGF (2000 U/kg daily for 2 weeks) or EPO (5000 U/kg daily for 2 weeks), respectively. Macroscopic, functional, electrophysiologic, ultraminiature, and histologic assessments of nerves were performed 4-8 weeks after surgery.. The results showed that in EPO-treated rats, there was a significant increase in the axon diameter, myelin thickness, and total number of nerve fibers as well as the degree of maturity of regenerated myelinated nerve fibers in comparison with those rats not treated with EPO. In addition, as measured by the SFI and MNCV, the motor function of the re-innervated hind limbs of rats with EPO treatment significantly improved at week 8, whereas there was no significant difference in the motor function between the 2 groups at 4 weeks.. Our results demonstrated that EPO is able to enhance nerve regeneration and promote functional recovery after peripheral nerve injury in the rat, suggesting the potential clinical application of EPO for the treatment of peripheral nerve injury in humans.

Topics: Animals; Cicatrix; Electrophysiology; Erythropoietin; Immunohistochemistry; Male; Microscopy, Electron; Motor Activity; Nerve Fibers; Nerve Regeneration; Rats; Rats, Sprague-Dawley; Recovery of Function; Sciatic Neuropathy; Ubiquitin Thiolesterase