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  • Title: Activation of apoptosis-linked caspase(s) in NMDA-injured brains in neonatal rats.
    Author: Nath R, Scott M, Nadimpalli R, Gupta R, Wang KK.
    Journal: Neurochem Int; 2000 Feb; 36(2):119-26. PubMed ID: 10676875.
    Abstract:
    Unilateral injection of 50 nmol of N-methyl-D-aspartate (NMDA) into the left posterior striatum of 7 day-old rat pups induces massive neuronal loss in the ipsilateral hemisphere in 5 days. In this model of excitotoxicity, the form of neuronal death (necrosis vs apoptosis) has not been clearly addressed. Here we report evidence of DNA laddering in the ipsilateral hemisphere 24 h after the NMDA injection. Activation of apoptosis-linked caspase(s) was also identified, as evidenced by (i) the formation of caspase-produced 120 kDa alpha-spectrin breakdown product (SBDP120) and (ii) increase in hydrolysis of caspase-3 substrate acetyl-DEVD-7-amido-4-methylcoumarin in the homogenate from the ipsilateral hemisphere. Lastly, we note that i.p. injection (100 mg/kg) of a pan caspase inhibitor Z-D-DCB attenuates the levels of SBDP120. Our results suggest the presence of caspase-activation in this rat pup model of NMDA toxicity.
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