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Correlation of hippocampal morphological changes and morris water maze performance after cortical contusion injury in rats

Clausen, Fredrik; Lewén, Anders; Marklund, Niklas LU ; Olsson, Yngve; McArthur, David L and Hillered, Lars (2005) In Neurosurgery 57(1). p.63-154
Abstract

OBJECTIVE: The hippocampus is essential to the processing and formation of memory. This study analyzed the relationship among memory dysfunction as revealed by Morris water maze (MWM) trial, cortical lesion volume, and regional hippocampal morphological changes after controlled cortical contusion (CCC). We also analyzed the influence of pretreatment with the nitrone radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN).

METHODS: Rats were subjected to CCC. We used two levels of CCC (mild, 1.5 mm and severe, 2.5 mm) and pretreated some severely injured animals with PBN. The animals were killed 15 days postinjury. We evaluated morphological changes to the hippocampus semiquantitatively by scoring sections immunohistochemically... (More)

OBJECTIVE: The hippocampus is essential to the processing and formation of memory. This study analyzed the relationship among memory dysfunction as revealed by Morris water maze (MWM) trial, cortical lesion volume, and regional hippocampal morphological changes after controlled cortical contusion (CCC). We also analyzed the influence of pretreatment with the nitrone radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN).

METHODS: Rats were subjected to CCC. We used two levels of CCC (mild, 1.5 mm and severe, 2.5 mm) and pretreated some severely injured animals with PBN. The animals were killed 15 days postinjury. We evaluated morphological changes to the hippocampus semiquantitatively by scoring sections immunohistochemically stained for microtubule-associated protein 2 with a four-point scale for the cornu ammonis (CA) 1, CA2, CA3, and hilus of the dentate gyrus (HDG). The cortical lesion volume was quantified.

RESULTS: Rats subjected to severe, but not mild, CCC demonstrated impaired spatial learning ability in the MWM, but this impairment was attenuated with pretreatment with the radical scavenger PBN. We documented bilateral morphological changes in CA1, CA3, and HDG and an ipsilateral neocortical cavitation in severely injured rats. PBN treatment attenuated (P < 0.05) the morphological characteristics of abnormality in the ipsilateral CA1, CA2, HDG, and the contralateral HDG and reduced the cortical lesion volume. Mild injury led to minor ipsilateral hippocampal and cortical damage but no MWM deficiency. Hippocampal morphological scores and total mean latencies in the MWM task were strongly correlated (r = 0.69; P < 0.001). The correlation between the cortical lesion volume and MWM latency was weaker (r = 0.48; P = 0.02).

CONCLUSION: Severe CCC causes bilateral morphological changes in the hippocampus and ipsilateral neocortical cavitation, which correlate to impairment in a spatial learning task (MWM). PBN protected the structure of the CA2 ipsilaterally and HDG bilaterally and reduced the cortical lesion volume, correlating to improved functional outcome.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Brain Concussion, Cell Count, Cerebral Cortex, Cyclic N-Oxides, Disease Models, Animal, Functional Laterality, Hippocampus, Immunohistochemistry, Male, Maze Learning, Microtubule-Associated Proteins, Neuroprotective Agents, Nitrogen Oxides, Rats, Rats, Sprague-Dawley, Statistics as Topic, Time Factors, Trauma Severity Indices, Comparative Study
in
Neurosurgery
volume
57
issue
1
pages
63 - 154
publisher
Congress of Neurological Surgeons
external identifiers
  • scopus:21744445217
ISSN
0069-4827
DOI
10.1227/01.NEU.0000163412.07546.57
language
English
LU publication?
no
id
6c6d0410-c920-43e7-af95-5077b2a05515
date added to LUP
2018-03-04 11:06:08
date last changed
2018-05-29 11:20:13
@article{6c6d0410-c920-43e7-af95-5077b2a05515,
  abstract     = {<p>OBJECTIVE: The hippocampus is essential to the processing and formation of memory. This study analyzed the relationship among memory dysfunction as revealed by Morris water maze (MWM) trial, cortical lesion volume, and regional hippocampal morphological changes after controlled cortical contusion (CCC). We also analyzed the influence of pretreatment with the nitrone radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN).</p><p>METHODS: Rats were subjected to CCC. We used two levels of CCC (mild, 1.5 mm and severe, 2.5 mm) and pretreated some severely injured animals with PBN. The animals were killed 15 days postinjury. We evaluated morphological changes to the hippocampus semiquantitatively by scoring sections immunohistochemically stained for microtubule-associated protein 2 with a four-point scale for the cornu ammonis (CA) 1, CA2, CA3, and hilus of the dentate gyrus (HDG). The cortical lesion volume was quantified.</p><p>RESULTS: Rats subjected to severe, but not mild, CCC demonstrated impaired spatial learning ability in the MWM, but this impairment was attenuated with pretreatment with the radical scavenger PBN. We documented bilateral morphological changes in CA1, CA3, and HDG and an ipsilateral neocortical cavitation in severely injured rats. PBN treatment attenuated (P &lt; 0.05) the morphological characteristics of abnormality in the ipsilateral CA1, CA2, HDG, and the contralateral HDG and reduced the cortical lesion volume. Mild injury led to minor ipsilateral hippocampal and cortical damage but no MWM deficiency. Hippocampal morphological scores and total mean latencies in the MWM task were strongly correlated (r = 0.69; P &lt; 0.001). The correlation between the cortical lesion volume and MWM latency was weaker (r = 0.48; P = 0.02).</p><p>CONCLUSION: Severe CCC causes bilateral morphological changes in the hippocampus and ipsilateral neocortical cavitation, which correlate to impairment in a spatial learning task (MWM). PBN protected the structure of the CA2 ipsilaterally and HDG bilaterally and reduced the cortical lesion volume, correlating to improved functional outcome.</p>},
  author       = {Clausen, Fredrik and Lewén, Anders and Marklund, Niklas and Olsson, Yngve and McArthur, David L and Hillered, Lars},
  issn         = {0069-4827},
  keyword      = {Animals,Brain Concussion,Cell Count,Cerebral Cortex,Cyclic N-Oxides,Disease Models, Animal,Functional Laterality,Hippocampus,Immunohistochemistry,Male,Maze Learning,Microtubule-Associated Proteins,Neuroprotective Agents,Nitrogen Oxides,Rats,Rats, Sprague-Dawley,Statistics as Topic,Time Factors,Trauma Severity Indices,Comparative Study},
  language     = {eng},
  number       = {1},
  pages        = {63--154},
  publisher    = {Congress of Neurological Surgeons},
  series       = {Neurosurgery},
  title        = {Correlation of hippocampal morphological changes and morris water maze performance after cortical contusion injury in rats},
  url          = {http://dx.doi.org/10.1227/01.NEU.0000163412.07546.57},
  volume       = {57},
  year         = {2005},
}