gms | German Medical Science

65th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

11 - 14 May 2014, Dresden

Dose-dependent effects of ethyl pyruvate on histological damage, inflammatory response and neurological deficits after controlled cortical impact (CCI) in the rat

Meeting Abstract

  • Nina Wenda - University of Mainz, Institute for Neurosurgical Pathophysiology, Mainz
  • Lisa Müller - University of Mainz, Institute for Neurosurgical Pathophysiology, Mainz
  • Daniel Jussen - University of Mainz, Institute for Neurosurgical Pathophysiology, Mainz
  • Axel Heimann - University of Mainz, Institute for Neurosurgical Pathophysiology, Mainz
  • Oliver Kempski - University of Mainz, Institute for Neurosurgical Pathophysiology, Mainz
  • Beat Alessandri - University of Mainz, Institute for Neurosurgical Pathophysiology, Mainz

Deutsche Gesellschaft für Neurochirurgie. 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Dresden, 11.-14.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocMI.15.01

doi: 10.3205/14dgnc352, urn:nbn:de:0183-14dgnc3526

Published: May 13, 2014

© 2014 Wenda et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Objective: The inflammatory response after traumatic brain injury (TBI) plays an important role for the development of trauma-associated cerebral damage. The prevention of this inflammatory reaction could therefore show neuroprotective potential.

Ethyl pyruvate (EP), a stable derivative of pyruvate, suppresses the inflammatory reaction after sepsis, hemorrhagic shock, cerebral ischemia and controlled cortical impact. Neuroprotective effects of intraperitoneal injections of EP acutely after CCI could be shown within 3 days after CCI but disappeared after one month of observation [1].

The aim of this study was to examine the dose-dependent effects of a long-term treatment with EP on histological damage, inflammatory response and functional recovery after CCI.

Method: Male Sprague-Dawley rats were anesthetized with chloral-hydrate and subjected to CCI (4 m/s, 200 ms, 2 mm). They were randomized in 5 groups: (1) Sham (no CCI, n=10), (2) CCI + vehicle (n=10), (3) CCI + 25 mg/kg EP (n=9), (4) CCI + 50 mg/kg EP (n=9), (5) CCI+ 75mg/kg EP (n=10). EP was injected 30 minutes after trauma and thereafter daily for 14 days. One day before brain-extraction, all animals were tested for neurological deficits (beam-walk- and beam-balance-test). The volume of the lesion was determined on hematoxylin-eosin stained brain sections, the inflammatory reaction was analyzed with immuno-staining for microglia (IBA), activated astrocytes (GFAP) and interleukine-1β.

Results: EP had no influence on CBF. Treatment with EP during 14 days showed no statistical significant reduction of the cortical damage although the group treated with 75 mg/kg EP showed the smallest lesions (Vehicle: 9,18 ± 1,17 mm3; 75 mg/kg: 7,31 ± 0,64 mm3). However, every dosage of EP led to a significant reduction of the neurological deficits after CCI. 75 mg/kg EP reduced slightly the immuno-reactive area of IL-1β and microglia (no statistical significance).

Conclusions: Long-term treatment with ethyl pyruvate improved the neurological deficits after CCI in every dosage but only the highest dose of 75 mg/kg EP tended to reduce the histological damage, the activation of microglia and the release of IL-1β.


References

1.
Moro N, Sutton RL. Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat. Exp Neurol. 2010 Oct;225(2):391-401. DOI: 10.1016/j.expneurol.2010.07.013 External link