TY - JOUR
T1 - Evaluation of the hematoma consequences, neurobehavioral profiles, and histopathology in a rat model of pontine hemorrhage
T2 - Laboratory investigation
AU - Lekic, Tim
AU - Rolland, William
AU - Manaenko, Anatol
AU - Krafft, Paul R.
AU - Kamper, Joel E.
AU - Suzuki, Hidenori
AU - Hartman, Richard E.
AU - Tang, Jiping
AU - Zhang, John H.
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PY - 2013/2
Y1 - 2013/2
N2 - Object. Primary pontine hemorrhage (PPH) represents approximately 7% of all intracerebral hemorrhages (ICHs) and is a clinical condition of which little is known. The aim of this study was to characterize the early brain injury, neurobehavioral outcome, and long-term histopathology in a novel preclinical rat model of PPH. Methods. The authors stereotactically infused collagenase (Type VII) into the ventral pontine tegmentum of the rats, in accordance with the most commonly affected clinical region. Measures of cerebrovascular permeability (brain water content, hemoglobin assay, Evans blue, collagen Type IV, ZO-1, and MMP-2 and MMP-9) and neurological deficit were quantified at 24 hours postinfusion (Experiment 1). Functional outcome was measured over a 30-day period using a vertebrobasilar scale (the modified Voetsch score), open field, wire suspension, beam balance, and inclined-plane tests (Experiment 2). Neurocognitive ability was determined at Week 3 using the rotarod (motor learning), T-maze (working memory), and water maze (spatial learning and memory) (Experiment 3), followed by histopathological analysis 1 week later (Experiment 4). Results. Stereotactic collagenase infusion caused dose-dependent elevations in hematoma volume, brain edema, neurological deficit, and blood-brain barrier rupture, while physiological variables remained stable. Functional outcomes mostly normalized by Week 3, whereas neurocognitive deficits paralleled the cystic cavitary lesion at 30 days. Obstructive hydrocephalus did not develop despite a clinically relevant 30-day mortality rate (approximately 54%). Conclusions. These results suggest that the model can mimic several translational aspects of pontine hemorrhage in humans and can be used in the evaluation of potential preclinical therapeutic interventions. © AANS, 2013.
AB - Object. Primary pontine hemorrhage (PPH) represents approximately 7% of all intracerebral hemorrhages (ICHs) and is a clinical condition of which little is known. The aim of this study was to characterize the early brain injury, neurobehavioral outcome, and long-term histopathology in a novel preclinical rat model of PPH. Methods. The authors stereotactically infused collagenase (Type VII) into the ventral pontine tegmentum of the rats, in accordance with the most commonly affected clinical region. Measures of cerebrovascular permeability (brain water content, hemoglobin assay, Evans blue, collagen Type IV, ZO-1, and MMP-2 and MMP-9) and neurological deficit were quantified at 24 hours postinfusion (Experiment 1). Functional outcome was measured over a 30-day period using a vertebrobasilar scale (the modified Voetsch score), open field, wire suspension, beam balance, and inclined-plane tests (Experiment 2). Neurocognitive ability was determined at Week 3 using the rotarod (motor learning), T-maze (working memory), and water maze (spatial learning and memory) (Experiment 3), followed by histopathological analysis 1 week later (Experiment 4). Results. Stereotactic collagenase infusion caused dose-dependent elevations in hematoma volume, brain edema, neurological deficit, and blood-brain barrier rupture, while physiological variables remained stable. Functional outcomes mostly normalized by Week 3, whereas neurocognitive deficits paralleled the cystic cavitary lesion at 30 days. Obstructive hydrocephalus did not develop despite a clinically relevant 30-day mortality rate (approximately 54%). Conclusions. These results suggest that the model can mimic several translational aspects of pontine hemorrhage in humans and can be used in the evaluation of potential preclinical therapeutic interventions. © AANS, 2013.
KW - Histopathology
KW - Neurobehavioral testing
KW - Pontine hemorrhage
KW - Rat
KW - Vascular disorders
KW - Brain Edema/chemically induced
KW - Cerebral Hemorrhage/chemically induced
KW - Rats
KW - Male
KW - Cognition
KW - Pons/blood supply
KW - Rats, Sprague-Dawley
KW - Disease Progression
KW - Behavior, Animal
KW - Hematoma/chemically induced
KW - Animals
KW - Blood-Brain Barrier/pathology
KW - Water/metabolism
KW - Collagenases/toxicity
KW - Disease Models, Animal
UR - http://www.scopus.com/inward/record.url?scp=84873667248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873667248&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/e9b5da74-e019-3c91-8bb2-b66b2c5774fb/
U2 - 10.3171/2012.10.JNS111836
DO - 10.3171/2012.10.JNS111836
M3 - Article
C2 - 23198805
SN - 0022-3085
VL - 118
SP - 465
EP - 477
JO - Journal of neurosurgery
JF - Journal of neurosurgery
IS - 2
ER -