Neuroscience 2004 Abstract
| Presentation Number: | 1019.18 |
|---|---|
| Abstract Title: | Protective effect of pyrrolidine dithiocarbamate in rat neonatal brain hypoxia/ischemia model. |
| Authors: |
Nurmi, A.*1,3
; Narvainen, J.2
; Goldsteins, G.1
; Grohn, O.2
; Koistinaho, J.1
1Dept of Neurobio, A.I. Virtanen Inst, Kuopio, Finland 2Dept of Biomed. NMR, A.I. Virtanen Inst, Kuopio, Finland 3Finland, Univ of Kuopio, 70211, |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Ischemia -- Neuroprotection and tolerance |
| Session: |
1019. Ischemia: Neuroprotection and Tolerance VII Poster |
| Presentation Time: | Wednesday, October 27, 2004 2:00 PM-3:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # YY8 |
| Keywords: | ANIMAL MODEL, NEURONAL DEATH, APOPTOSIS |
Brain hypoxia/ischemia (H/I) triggers several pathophysiological mechanisms, which contribute to the neuronal damage in immature brain. An important regulator of post-ischemic inflammation as well as pro- and anti-apoptotic gene expression is the transcription factor nuclear factor kappa-B (NF-κB), which has been shown to be involved in models of ischemic insults of the adult brain. However, very little is known about the role of NF-κB and its role in ischemia models of neonatal brain. We therefore studied the effect of pyrrolidine dithiocarbamate (PDTC), an established inhibitor of NF-κB, which previously has been found to be protective in adult brain ischemia, in a rat model of neonatal brain hypoxia/ischemia (H/I).
Exposure to H/I produced brain infarcts as evidenced by T2- weighed magnetic resonance imaging (T2-MRI) 7 days after the insult in P7 Wistar rats. A single dose (50 mg/kg, i.p.) of PDTC 2 hours after the H/I insult reduced the mean brain infarct size by 59 %. Immunohistochemical analysis of H/I brains revealed strong immunoreactivity against p65 subunit of NF-κB in the ipsilateral hemisphere 6 and 48 hours after the H/I insult. In PDTC treated rats p65 immunoreactivity was strongly inhibited, especially 6 hours after the insult. Western blot analysis and immunohistochemical data revealed significantly increased levels of cleaved caspase-3 in the ipsilateral hemisphere 24 hours and 7 days after the insult. Treatment with PDTC prevented the increased expression of cleaved caspase-3 in the ipsilateral hemisphere at 24 hours, but had no effect 7 days after the insult.
These results suggest that acutely administered PDTC provides protection in the immature brain and protection may be related to anti-apoptotic effects via inhibition of NF-κB regulated pathways.
Exposure to H/I produced brain infarcts as evidenced by T2- weighed magnetic resonance imaging (T2-MRI) 7 days after the insult in P7 Wistar rats. A single dose (50 mg/kg, i.p.) of PDTC 2 hours after the H/I insult reduced the mean brain infarct size by 59 %. Immunohistochemical analysis of H/I brains revealed strong immunoreactivity against p65 subunit of NF-κB in the ipsilateral hemisphere 6 and 48 hours after the H/I insult. In PDTC treated rats p65 immunoreactivity was strongly inhibited, especially 6 hours after the insult. Western blot analysis and immunohistochemical data revealed significantly increased levels of cleaved caspase-3 in the ipsilateral hemisphere 24 hours and 7 days after the insult. Treatment with PDTC prevented the increased expression of cleaved caspase-3 in the ipsilateral hemisphere at 24 hours, but had no effect 7 days after the insult.
These results suggest that acutely administered PDTC provides protection in the immature brain and protection may be related to anti-apoptotic effects via inhibition of NF-κB regulated pathways.
Supported by Finland’s Academy and Ministry of Education, Finland
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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