Temporal changes in intracranial pressure in a modified experimental model of closed head injury

Restricted access

Object. The authors describe an experimental model of closed head injury in rodents that was modified from one developed by Marmarou and colleagues. This modification allows dual control of the dynamic process of impact compared with impulse loading that occurs at the moment of primary brain injury. The principal element in this weight-drop model is an adjustable table that supports the rat at the moment of impact from weights positioned at different heights (accelerations). The aim was to obtain reproducible pathological intracranial pressure (ICPs) while maximally reducing the incidence of mortality and skull fractures.

Methods. Intracranial pressure was investigated in different experimental settings, including two different rat strains and various impact-acceleration conditions and posttrauma survival times. Identical impact-acceleration injuries produced a considerably higher mortality rate in Wistar rats than in Sprague—Dawley rats (50% and 0%, respectively). Gradually increasing severity of impact-acceleration conditions resulted in findings of a significant correlation between the degree of traumatic challenge and increased ICP at 4 hours (p < 0.001, R2 = 0.73). When the impact-acceleration ratio was changed to result in a more severe head injury, the ICP at 4, 24, and 72 hours was significantly elevated in comparison with that seen in sham-injured rats (4 hours: 19.7 ± 2.8 mm Hg, p = 0.004; 24 hours: 21.8 ± 1.1 mm Hg, p = 0.002; 72 hours: 11.9 ± 2.5 mm Hg, p = 0.009). Comparison of the rise in ICP between moderate and severe impact-acceleration injury at 4 and 24 hours revealed a significantly higher value after severe injury (4 hours: p = 0.008; 24 hours: p = 0.004). Continuous recordings showed that ICP mounted very rapidly to peak values, which declined gradually toward a pathological level dependent on the severity of the primary insult. Histological examination after severe trauma revealed evidence of irreversible neuronal necrosis, diffuse axonal injury, petechial bleeding, glial swelling, and perivascular edema.

Conclusions. This modified closed head injury model mimics several clinical features of traumatic injury and produces reliable, predictable, and reproducible ICP elevations with concomitant morphological alterations.

Article Information

Address reprint requests to: Koen Engelborghs, M.D., Department of Neurosurgery, University Hospital Antwerp, Wilrijkstraat 10, B—2650, Edegem, Belgium.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Photographs showing the head injury device (a) and detail of the horizontal platform (b). The upper part consists of a hollow plexiglass column (1) perforated at regular intervals (2) to permit weight drops from various heights. The weight (3) is fixed by means of a nylon string, which passes through a smooth central aperture of a metal lid (4). An automatic security device (5) is provided at the bottom to prevent rebound impact of the cylinder. The whole apparatus is firmly fixed to a horizontal base (6) and precisely leveled. b: Detail of the rigid plastic horizontal platform (7) mounted on replaceable springs of variable elasticity (8) assembled in a plexiglass chamber (9). At both sides of the chamber, a stereotactic apparatus (10) and two soft foam cushions (11) are attached to allow accurate positioning of the rat. Three velcro strips (12) are used to secure the animal on the platform.

  • View in gallery

    Bar graph showing increase in ICP in Wistar and Sprague—Dawley rats at 4 hours after similar impact-acceleration trauma (400 g, 60 cm, k = 2206 N/m; mean ± SEM, 10 rats/group).

  • View in gallery

    Bar graph showing measurements obtained 4 hours after gradually increasing impact-acceleration challenge (height = 0–55 cm, 400 g, k = 2206 N/m) that showed a significant correlation between the severity of traumatic challenge and a rise in ICP in Sprague—Dawley rats (slope of ICP/height = 4.9 ± 0.02 mm Hg/cm, p < 0.001; R2 = 0.73; six rats/group, mean ± SEM).

  • View in gallery

    Bar graph showing changes in ICP, CPP, and MABP at different times after severe impact-acceleration injury in comparison with sham-injured rats (mean ± SEM; six rats/group; +p , 0.005; *p , 0.01; xp < 0.05).

  • View in gallery

    Bar graph comparing ICP values at 4 and 24 hours after moderate trauma (MT) and severe trauma (ST) and showing a significantly higher ICP in the severe trauma group (mean ± SEM; six rats/group; *p = 0.009; +p = 0.004).

  • View in gallery

    Graph showing continuous ICP recordings (mean ± SEM) during 4 hours in rats subjected to moderate (open circles; six rats) and severe impact-acceleration trauma (closed triangles; six rats) compared with sham-injured rats (closed circles; three rats).

  • View in gallery

    Graphs showing MABP response at different times after severe impact-acceleration trauma. Upper: The MABP response over the first 30 seconds. A brief increase lasting 2 to 3 seconds (106 ± 6.9 mm Hg; p = 0.34) is followed by a relatively constant decline over the next 17 seconds (69.5 ± 4.1 mm Hg; p < 0.001). There is no indication of a hypertensive surge (mean ± SEM; six rats). Lower: The MABP course over 4 hours after severe impact-acceleration trauma. The MABP gradually recovers to baseline values (104.3 ± 3.4 mm Hg) within 50 to 55 minutes (96.6 ± 2.2 mm Hg; p = 0.17). Four hours after head injury MABP is significantly lower in comparison with preinjury values (84.4 ± 4.2 mm Hg; p = 0.014).

  • View in gallery

    Light microscopy studies of medial thalamic nucleus (a and b), internal capsule (c), and optical tract (d and e) in sham-injured rats (a and d) and rats subjected to severe trauma that survived 4 hours (b), 24 hours (c), and 72 hours (e). a: In nontraumatized brain, neurons (N) and microvessels (V) exhibit a normal morphological aspect. They are embedded in a compact neuropil composed of normal-shaped unmyelinated (arrowhead) and myelinated cell processes (arrow). b: Four hours postinjury, several neurons appear to be shrunken with pyknotic nuclei (arrows), whereas others are well preserved (N). Microvessels appear slightly compressed by swollen glial cell processes, which are also found throughout the neuropil and around neurons (asterisks). A number of myelinated axons show typical ballooning (arrowhead). c: At 24 hours axonal ballooning is more pronounced, leading to a disorganized aspect of white matter. Next to well-preserved axons (arrows) many axons are extremely swollen and have lost their axonal content (arrowheads). d and e: White matter disorganization was also found after 72 hours (e) in the optic tract (OT) as a result of axonal ballooning and myelin disintegration, a phenomenon that is not seen in uninjured rats (d). Toluidine blue, original magnification × 800 (a—c); × 280 (d and e).

  • View in gallery

    Electron micrographs from medial thalamic nucleus 4 hours after severe trauma. a: Neurons with a pyknotic nucleus (n) and a completely disorganized cytoplasm with dense mitochondria (m) are seen. The surrounding neuropil is characterized by extremely swollen processes that are probably of glial origin (asterisks). Myelinized axons (ax) and nonmyelinized cell processes (p) are relatively well preserved. b: Axonal ballooning can be recognized by extremely dilated axons (ab) that contain a core of neurofilaments (nf) surrounded by a region with accumulations of vesicular material (arrowhead) and mitochondria. Surrounding neurons (N), myelinized axons, and synapses (s) are relatively well preserved, whereas glial cell processes appear swollen (asterisk). Original magnification × 8000.

References

  • 1.

    Barzó PMarmarou AFatouros Pet al: Magnetic resonance imaging—monitored acute blood brain barrier changes in experimental traumatic brain injury. J Neurosurg 85:111311211996Barzó P Marmarou A Fatouros P et al: Magnetic resonance imaging—monitored acute blood brain barrier changes in experimental traumatic brain injury. J Neurosurg 85:1113–1121 1996

    • Search Google Scholar
    • Export Citation
  • 2.

    Bullock RChesnut RMClifton Get al: Guidelines for the management of severe head injury. J Neurotrauma 13:6437341996Bullock R Chesnut RM Clifton G et al: Guidelines for the management of severe head injury. J Neurotrauma 13:643–734 1996

    • Search Google Scholar
    • Export Citation
  • 3.

    Cortez SCMcIntosh TKNoble LJ: Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res 482:2712821989Cortez SC McIntosh TK Noble LJ: Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res 482:271–282 1989

    • Search Google Scholar
    • Export Citation
  • 4.

    Dixon CELighthall JWAnderson TE: Physiologic, histopathologic and cineradiographic characterization of a new fluid-percussion model of experimental brain injury in the rat. J Neurotrauma 5:911041988Dixon CE Lighthall JW Anderson TE: Physiologic histopathologic and cineradiographic characterization of a new fluid-percussion model of experimental brain injury in the rat. J Neurotrauma 5:91–104 1988

    • Search Google Scholar
    • Export Citation
  • 5.

    Dixon CELyeth BGPovlishock JTet al: A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:1101191987Dixon CE Lyeth BG Povlishock JT et al: A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:110–119 1987

    • Search Google Scholar
    • Export Citation
  • 6.

    Engelborghs KVerlooy JVan Reempts Jet al: Intracranial pressure in a modified experimental model of closed head injury. Acta Neurochir Suppl 70:1231251997Engelborghs K Verlooy J Van Reempts J et al: Intracranial pressure in a modified experimental model of closed head injury. Acta Neurochir Suppl 70:123–125 1997

    • Search Google Scholar
    • Export Citation
  • 7.

    Foda MAAEMarmarou A: A new model of diffuse brain injury in rats. Part II: Morphological characterization. J Neurosurg 80:3013131994Foda MAAE Marmarou A: A new model of diffuse brain injury in rats. Part II: Morphological characterization. J Neurosurg 80:301–313 1994

    • Search Google Scholar
    • Export Citation
  • 8.

    Gennarelli TA: Animate models of human head injury. J Neurotrauma 11:3573681994Gennarelli TA: Animate models of human head injury. J Neurotrauma 11:357–368 1994

    • Search Google Scholar
    • Export Citation
  • 9.

    Gennarelli TAThibault LEAdams JHet al: Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 12:5645741982Gennarelli TA Thibault LE Adams JH et al: Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 12:564–574 1982

    • Search Google Scholar
    • Export Citation
  • 10.

    Goldstein M: Traumatic brain injury: a silent epidemic. Ann Neurol 27:3271990Goldstein M: Traumatic brain injury: a silent epidemic. Ann Neurol 27:327 1990

    • Search Google Scholar
    • Export Citation
  • 11.

    Ito JMarmarou ABarzó Pet al: Characterization of edema by diffusion weighted imaging in experimental traumatic brain injury. J Neurosurg 84:971031996Ito J Marmarou A Barzó P et al: Characterization of edema by diffusion weighted imaging in experimental traumatic brain injury. J Neurosurg 84:97–103 1996

    • Search Google Scholar
    • Export Citation
  • 12.

    Lewis SBFinnie JWBlumbergs PCet al: A head impact model of early axonal injury in the sheep. J Neurotrauma 13:5055141996Lewis SB Finnie JW Blumbergs PC et al: A head impact model of early axonal injury in the sheep. J Neurotrauma 13:505–514 1996

    • Search Google Scholar
    • Export Citation
  • 13.

    Lighthall JWAnderson TE: In vivo models of experimental brain and spinal cord trauma in Salzman SKFaden IA (eds): The Neurobiology of Central Nervous System Trauma. New York: Oxford University Press1994 pp 311Lighthall JW Anderson TE: In vivo models of experimental brain and spinal cord trauma in Salzman SK Faden IA (eds): The Neurobiology of Central Nervous System Trauma. New York: Oxford University Press 1994 pp 3–11

    • Search Google Scholar
    • Export Citation
  • 14.

    Marmarou AFoda MAAEvan den Brink Wet al: A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 80:2913001994Marmarou A Foda MAAE van den Brink W et al: A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 80:291–300 1994

    • Search Google Scholar
    • Export Citation
  • 15.

    Marshall LFMarshall SBKlauber MRet al: The diagnosis of head injury requires a classification based on computed axial tomography. J Neurotrauma Suppl 1:S287S2921992Marshall LF Marshall SB Klauber MR et al: The diagnosis of head injury requires a classification based on computed axial tomography. J Neurotrauma Suppl 1:S287–S292 1992

    • Search Google Scholar
    • Export Citation
  • 16.

    McIntosh TKNobel LAndrews Bet al: Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. Cent Nerv Syst Trauma 4:1191341987McIntosh TK Nobel L Andrews B et al: Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. Cent Nerv Syst Trauma 4:119–134 1987

    • Search Google Scholar
    • Export Citation
  • 17.

    Ommaya AKGennarelli TA: Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observation on blunt head injuries. Brain 97:6336541974Ommaya AK Gennarelli TA: Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observation on blunt head injuries. Brain 97:633–654 1974

    • Search Google Scholar
    • Export Citation
  • 18.

    Ommaya AKRockoff SDBaldwin M: Experimental concussion. J Neurosurg 21:2492641964Ommaya AK Rockoff SD Baldwin M: Experimental concussion. J Neurosurg 21:249–264 1964

    • Search Google Scholar
    • Export Citation
  • 19.

    Paxinos GWatson C: The Rat Brain in Stereotaxic Coordinatesed 2. Sydney: Academic Press1986Paxinos G Watson C: The Rat Brain in Stereotaxic Coordinates ed 2. Sydney: Academic Press 1986

    • Search Google Scholar
    • Export Citation
  • 20.

    Pfenninger EGReith ABreitig Det al: Early changes of intracranial pressure, perfusion pressure, and blood flow after acute head injury. Part 1: an experimental study of the underlying pathophysiology. J Neurosurg 70:7747791989Pfenninger EG Reith A Breitig D et al: Early changes of intracranial pressure perfusion pressure and blood flow after acute head injury. Part 1: an experimental study of the underlying pathophysiology. J Neurosurg 70:774–779 1989

    • Search Google Scholar
    • Export Citation
  • 21.

    Piper IRThompson DMiller JD: Monitoring weight drop velocity and foam stiffness as an aid to quality control of a rodent model of impact acceleration neurotrauma. J Neurosci Methods 69:1711741996Piper IR Thompson D Miller JD: Monitoring weight drop velocity and foam stiffness as an aid to quality control of a rodent model of impact acceleration neurotrauma. J Neurosci Methods 69:171–174 1996

    • Search Google Scholar
    • Export Citation
  • 22.

    Shima KMarmarou A: Evaluation of brain-stem dysfunction following severe fluid percussion head injury to the cat. J Neurosurg 74:2702771991Shima K Marmarou A: Evaluation of brain-stem dysfunction following severe fluid percussion head injury to the cat. J Neurosurg 74:270–277 1991

    • Search Google Scholar
    • Export Citation
  • 23.

    Stalhammar DGralinat BJAllen AMet al: A new model of concussive brain injury in the cat produced by extradural fluid volume loading. Brain Inj 1:931121987Stalhammar D Gralinat BJ Allen AM et al: A new model of concussive brain injury in the cat produced by extradural fluid volume loading. Brain Inj 1:93–112 1987

    • Search Google Scholar
    • Export Citation
  • 24.

    Yoshino EYamaki THiguchi Tet al: Acute brain edema in fatal head injury: analysis by dynamic CT scanning. J Neurosurg 63:8308391985Yoshino E Yamaki T Higuchi T et al: Acute brain edema in fatal head injury: analysis by dynamic CT scanning. J Neurosurg 63:830–839 1985

    • Search Google Scholar
    • Export Citation

TrendMD

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 66 66 3
Full Text Views 154 154 0
PDF Downloads 77 77 0
EPUB Downloads 0 0 0

PubMed

Google Scholar