Neuroscience 2005 Abstract
| Presentation Number: | 222.9 |
|---|---|
| Abstract Title: | Minocycline decreases activated microglia in hypoxic/ischemic cerebral white matter of immature rat. |
| Authors: |
Lechpammer, M.*1
; Samonte, F.1
; Talos, D.1
; Volpe, J. J.1
; Jensen, F. E.1
1Dept. of Neurology, Children's Hospital, Harvard Medical School, Boston, MA |
| Primary Theme and Topics |
Disorders of the Nervous System - Ischemia -- Cellular and molecular mechanisms: Oxidative stress and neuroinflammatory response |
| Session: |
222. Hypoxic/Ischemic Injury in the Developing Brain Poster |
| Presentation Time: | Sunday, November 13, 2005 8:00 AM-9:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # UU85 |
| Keywords: | microglia, hypoxia, ischemia, minocycline |
Periventricular leukomalacia (PVL) is due to oligodendrocyte (OL) injury and hypomyelination associated with hypoxia/ischemia (H/I) and systemic inflammation in premature infants. Using immature rodent model of H/I white matter (WM) injury, we shown that early OL injury occurs due to glutamate-receptor mediated toxicity and can be attenuated by AMPAR antagonists (Follett, J. Nsci, 2004). Activated microglia play an active role in the inflammatory response following the cerebral injury, and we showed a steady increase in microglia 24–72 hrs following H/I (Samonte, SFN Abs, 2004). In this study, we examined in the same model the protective efficacy of the microglial inactivator minocycline administered post H/I. Postnatal day 6 Long-Evans rats underwent left carotid artery ligation, followed by a hypoxia (1hr, 6%O2), and were randomly divided into minocycline-treated (n=8) and control groups (n=8). Minocycline treatment (50mg/kg i.p.) was initiated immediately following H/I and continued every 12 hrs. The control group received only PBS at the same time points. Animals were sacrificed at 72 and 96 hrs and compared to controls. Microglia were stained immunocytochemically (CD68), and cells were counted in pericallosal WM ipsilateral and contralateral to the ligation. In addition, myelin basic protein (MBP) was examined in pericallosal WM. Minocycline treatment significantly decreased the number of CD68+ microglia at 96 hrs ipsilateral to the lesion (31 cells/60 µm2) compared to untreated H/I controls (41cells/60 µm2, p=0.02). There was also modest preservation of MBP staining at 96 hrs compared to untreated animals subjected to H/I (p=0.03). These data suggest that microglial activation following H/I causes delayed OL death at the lesion site, and that minocycline reduces the microglial number and OL injury. Anti-inflammatory or antimicroglial agents may have a role in the treatment of PVL, possibly in combination with AMPAR antagonists.
Supported by T32 NS007473, NS31718, NS38475, HD18655, United Cerebral Palsy Fndt
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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