Morris water maze function and histologic characterization of two age-at-injury experimental models of controlled cortical impact in the immature rat
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Controlled cortical impact (CCI) is commonly used in adult animals to study focal traumatic brain injury (TBI). Our study aims to further study injury mechanisms in children and variable models of pathology in the developing brain.
Develop a focal injury model of experimental TBI in the immature, postnatal days (PND) 7 and 17 rats that underwent a CCI at varying depths of deflection, 1.5–2.5 mm compared with sham and then tested using the Morris water maze (MWM) beginning on post-injury day (PID) 11. Histopathologic analysis was performed at PID 1 and 28.
In PND 7, the 1.75- and 2.0-mm deflections (diameter (d) = 3 mm; velocity = 4 m/s; and duration = 500 ms) resulted in significant MWM deficits while the 1.5-mm injury did not produce MWM deficits vs. sham controls. In PND 17, all injury levels resulted in significant MWM deficits vs. sham controls with a graded response; the 1.5-mm deflection (d = 6 mm; velocity = 4 m/s; and duration = 500 ms) produced significantly less deficits as compared WITH the 2.0- and 2.5-mm injuries. Histologically, a graded injury response was also seen in both ages at injury with cortical and more severe injuries, hippocampal damage. Cortical contusion volume increased in most injury severities from PID 1 to 28 in both ages at injury while hippocampal volumes subsequently decreased.
CCI in PND 7 and 17 rat results in significant MWM deficits and cortical histopathology providing two different and unique experimental models of TBI in immature rats that may be useful in further investigations into the mechanisms and treatments of pediatric TBI.
KeywordsAge Animal studies Models of injury Pediatric brain injury Traumatic brain injury
The authors wish to thank the National Institute of Health for its support for PDA (NIH RO1 NS42298) and PMK (NIH RO1 NS 30318 and NS 38087). The authors also wish to thank Ms. Christina Casanova for her help in the manuscript preparation.
- 2.Adelson PD, Bratton SL, Carney NA, Chesnut RM, du Coudray HE, Goldstein B, Kochanek PM, Miller HC, Partington MD, Selden NR, Warden CR, Wright DW (2003) Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Pediatr Crit Care Med 4(3 Suppl):S1–S75Google Scholar
- 11.Bayir H, Tyurin VA, Tyurina YY, Viner R, Ritov V, Amoscato AA, Zhao Q, Zhang XJ, Janesko-Feldman KL, Alexander H, Basova LV, Clark RS, Kochanek PM, Kagan VE (2007) Selective early cardiolipin peroxidation after traumatic brain injury: an oxidative lipidomics analysis. Ann Neurol 62(2):154–169PubMedCrossRefGoogle Scholar
- 12.Berger-Sweeney J, Heckers S, Mesulam MM, Wiley RG, Lappi DA, Sharma M (1994) Differential effects on spatial navigation of immunotoxin-induced cholinergic lesions of the medial septal area and nucleus basalis magnocellularis. J Neurosci: Off J Soc Neurosci 14(7):4507–4519Google Scholar
- 14.Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger JE (2006) Guidelines for the surgical management of traumatic brain injury. Neurosurgery 58(3 Suppl):S2-ivGoogle Scholar
- 19.Dixon CE, Markgraf CG, Angileri F, Pike BR, Wolfson B, Newcomb JK, Bismar MM, Blanco AJ, Clifton GL, Hayes RL (1998) Protective effects of moderate hypothermia on behavioral deficits but not necrotic cavitation following cortical impact injury in the rat. J Neurotrauma 15(2):95–103PubMedCrossRefGoogle Scholar
- 33.Jenkins LW, Peters GW, Dixon CE, Zhang X, Clark RS, Skinner JC, Marion DW, Adelson PD, Kochanek PM (2002) Conventional and functional proteomics using large format two-dimensional gel electrophoresis 24 hours after controlled cortical impact in postnatal day 17 rats. J Neurotrauma 19(6):715–740PubMedCrossRefGoogle Scholar
- 37.Kochanek PM, Carney N, Adelson PD, Ashwal S, Bell MJ, Bratton S, Carson S, Chesnut RM, Ghajar J, Goldstein B, Grant GA, Kissoon N, Peterson K, Selden NR, Tasker RC, Tong KA, Vavilala MS, Wainwright MS, Warden CR (2012) Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents—second edition. Pediatric Crit Care Med 13(Suppl 1):S1–S82Google Scholar
- 39.Kraus JF (1987) Epidemiology of head injury. In: Cooper PR (ed) Head injury. Williams and Wilkins, Baltimore, pp 1–19Google Scholar
- 40.Kraus JF (1995) Epidemiological features of brain injury in children: occurrence, children at risk, causes and manner of injury, severity, and outcomes. In: Broman SH, Michel ME (eds) Traumatic head injury in children. Oxford University Press, New York, pp 22–39Google Scholar
- 43.Levin HS, Ewing-Cobbs L, Eisenberg HM (1995) Neurobehavioral outcome of pediatric closed head injury. In: Broman SH, Michel M (eds) Traumatic head injury in children. Oxford University Press, New York, pp 70–94Google Scholar
- 64.Stevenson KL, Davis DS, Skinner JC, Tran MP, Dixon CE, Kochanek PM, Jenkins LW, Adelson PD (2000) Behavioral dysfunction in immature rats after controlled cortical impact. [Abstract]. J Neurotrauma 17(10):944Google Scholar