Spinal cord contusion injury is one of the most serious nervous system disorders, characterized by high morbidity and disability. To mimic spinal cord contusion in humans, various animal models of spinal contusion injury have been developed. These models have been developed in rats, mice, and monkeys. However, most of these models are developed using rats. Two types of animal models, i.e. bilateral contusion injury and unilateral contusion injury models, are developed using either a weight drop method or impactor method. In the weight drop method, a specific weight or a rod, having a specific weight and diameter, is dropped from a specific height on to the exposed spinal cord. Low intensity injury is produced by dropping a 5 g weight from a height of 8 cm, moderate injury by dropping 10 g weight from a height of 12.5–25 mm, and high intensity injury by dropping a 25 g weight from a height of 50 mm. In the impactor method, injury is produced through an impactor by delivering a specific force to the exposed spinal cord area. Mild injury is produced by delivering 100 ± 5 kdyn of force, moderate injury by delivering 200 ± 10 kdyn of force, and severe injury by delivering 300 ± 10 kdyn of force. The contusion injury produces a significant development of locomotor dysfunction, which is generally evident from the 0–14
th
day of surgery and is at its peak after the 28–56
th
day. The present review discusses different animal models of spinal contusion injury.
Adenosine preconditioning may increase the release of nitric oxide, which in turn may increase the release of cysteinyl leukotrienes to confer cardioprotection.
The aging process induces a plethora of changes in the body including alterations in hormonal regulation and metabolism in various organs including the heart. Aging is associated with marked increase in the vulnerability of the heart to ischemia-reperfusion injury. Furthermore, it significantly hampers the development of adaptive response to various forms of conditioning stimuli (pre/post/remote conditioning). Aging significantly impairs the activation of signaling pathways that mediate preconditioning-induced cardioprotection. It possibly impairs the uptake and release of adenosine, decreases the number of adenosine transporter sites and down-regulates the transcription of adenosine receptors in the myocardium to attenuate adenosine-mediated cardioprotection. Furthermore, aging decreases the expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) and subsequent transcription of catalase enzyme which subsequently increases the oxidative stress and decreases the responsiveness to preconditioning stimuli in the senescent diabetic hearts. In addition, in the aged rat hearts, the conditioning stimulus fails to phosphorylate Akt kinase that is required for mediating cardioprotective signaling in the heart. Moreover, aging increases the concentration of Na+ and K+, connexin expression and caveolin abundance in the myocardium and increases the susceptibility to ischemia-reperfusion injury. In addition, aging also reduces the responsiveness to conditioning stimuli possibly due to reduced kinase signaling and reduced STAT-3 phosphorylation. However, aging is associated with an increase in MKP-1 phosphorylation, which dephosphorylates (deactivates) mitogen activated protein kinase that is involved in cardioprotective signaling. The present review describes aging as one of the major confounding factors in attenuating remote ischemic preconditioning-induced cardioprotection along with the possible mechanisms.
The influence of maternal phenotype was observed in 471 consecutive sib pairs to explore the segregation distortions for the ABO system. The ABO typing was done using the standard technique of haemagglutination reaction and the sib pairs were named according to their phenotypes. Thus A-B is the pair where first sib was A and the consecutive one was B. The statistical computations involved calculations of ABO gene frequencies, and application of chi-square and Z test for proportions to study the segregation distortions in sibs. A significant excess of B gene in the first sib and reduction of O in the second sib was observed when the Z test was applied to study the covariance, whereas no significant distortions were observed with simple Chi-square test. Heterozygote AO mothers segregated insignificantly in favour of A allele whereas BO mothers segregated significantly in favour of B allele in the first as well as in the second sib indicating that selection is favouring the B gene in our population.
Aim:To study the effect of 3-methyladenine and chloroquine phosphate on 3-nitropropionic acid induced Huntington's disease-like symptoms in mice. Materials and Methods: 3-Nitropropionic acid was administered at the dose of 50 mg/kg, i.p. twice daily for 5 days for inducing Huntington's disease like symptoms. 3-Methyladenine (15 and 30 mg/kg, i.p.) and chloroquine phosphate (25 and 50 mg/kg, i.p.) were administered 30 min before each 3-nitropropionic acid administration. The motor tests including, rota-rod, beam walking, lateral push test and open-field test, along with memory/cognitive test using object recognition test were performed on day 0, 3 and 6. The role of autophagy was assessed by measuring the levels of LC3II in the brain. Histopathological studies using H&E, nissl staining; and immunohistochemistry of neuron specific enolase and caspase-3 were also performed. Results: Administration of 3-nitropropionic acid caused a decline in the motor functions and cognitive abilities of the animals. The histopathological studies also indicated neuronal injury and neuronal loss in the striatal region. Treatment with 3-methyladenine and chloroquine ameliorated motor and cognitive parameters induced by 3-nitropropionic acid along with prevention of neuronal loss. Moreover, these pharmacological agents ameliorated altered levels of LC3II with 3-methyladenine and chloroquine administration indicated involvement of autophagy. Conclusion: Treatment with 3-methyladenine and chloroquine may improve the symptoms related with Huntington's disease by preventing 3-nitropropionic acid-induced neurodegeneration possibly by inhibiting autophagy.
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