Summary
To evaluate the potency of putative secondary mediators of brain edema and their possible contribution to edema related brain dysfunction an infusion model of brain edema was developed in rats. 100 ul of fluid (saline, 20% nonautologous protein) was infused over one hour into the left forebrain white matter through a stereotaxically placed (+ 1.2 mm ant to bregma, 3 mm lateral and 2.9 mm depth) 25 G needle. Brain tissue hydraulic resistance (Rt), regional cerebral blood flow (rCBF), cortical somatosensory evoked potentials (SEPs) and intracranial pressure (ICP) (intraventricular needle) were monitored during the infusion and rCBF CO2 reactivity (hydrogen clearance), local brain water content (microgravimetry), BBB integrity (Evans Blue 2%) and brain histology (H & E, Solochrome-cyanin) were evaluated after the infusion. Saline infusates caused no physiological dysfunction despite ipsilateral expansion and vacuolation of the subcortical white matter, separation of axonal bundles and a significant decrease (p=3.8×10−5)in local subcortical tissue specific gravity. Cortical histology and specific gravity adjacent to the infusion locus were normal. Rt significantly decreased (p=6.5×10−4) during the infusion but there were only minor increases in ICP. Findings with 20% protein infusates were similar despite a focal 65% decrement in the rCBF CO2 reactivity adjacent to the infusion site. This study has shown that a simple and inexpensive model of infusion brain edema can be created in the rat and that it provides a useful model for assessing the physiological effects of mediator compounds in the infusate. Potential applications and methodological improvements for this model are discussed.
Similar content being viewed by others
References
Allison T, Wood CC, McCarthy Det al (1982) Short latency somatosensory evoked potentials in man, monkey, cat and rat: comparative latency analysis. In: Courjon J, Mauguiere F, Revol M (eds) Clinical applications of evoked potentials in neurology, Raven press, New York, pp 304–311
Aritake K, Nakai S, Asano A, Takakura K, Brock M (1983) Peroxidation of arachidonic acid and brain oedema. J CBF Metab 3 [Suppl 1]: S297–298
Baethmann A, Oettinger W, Rothenfusser O, Kempski O, Unterberg A, Geiger R (1980) Brain edema factors: Current state with particuler reference to plasma constituents and glutamate. Adv Neurol 28: 171–195
Bell BA, Foubister GC, Neto F, Miller JD (1985) The effect of experimental common carotid arteriotomy on cerebral blood flow in the rat. Neurosurgery 16: 322–326
—, Smith MA, Kean DM, McGhee CNJ, MacDonald HL, Miller JD, Barnett GH, Tocher JL, Douglas RHB, Best J (1987) Brain water measured by magnetic resonance imaging. Correlation with direct estimation and changes after mannitol and dexamethasone. Lancet i: 66–69
Benveniste H, Diemer NH (1987) Cellular reactions to implantation of a microdialysis tube in the rat hippocampus. Acta Neuropath (Berl) 74: 234–238
Benveniste H, Drejer J, Schousboe A, Diemer N (1987) Regional cerebral glucose phosphorylation and blood flow after insertion of a microdialysis fiber through the dorsal hippocampus of the rat. J Neurochem 49: 729–734
Black KL, Hoff JT (1985) Leukotrienes increase blood brain barrier permeability following intraparenchymal injections in rats. Ann Neurol 18: 349–351
Bodsch W, Rommel T, Ophoff BG, Menzel J (1987) Factors responsible for the retention of fluid in human tumor edema and the effect of dexamethasone. J Neurosurg 67: 250–257
Boksa P, Mykita S, Collier B (1988) Arachidonic acid inhibits choline uptake and depletes acetylcholine content in rat cerebral cortical synaptosomes. J Neurochem 50: 1309–1318
Bothe H WW, Bodsch W, Hossmann KA (1984) Relationship between specific gravity, water content and serum protein extravastion in various types of vasogenic brain edema. Acta Neuropath (Berl) 64: 37–42
Brett M, Weller RO (1978) Intracellular serum proteins in cerebral gliomas and metastatic tumours; an immunoperoxidase study. Neuropath Appl Neurobiol 4: 263–272
Chan PH, Fishmann RA, Caronna J, Schmidly JW, Lee J (1983) Induction of brain edema following intracerebral injection of arachidonic acid. Ann Neurol 13: 625–632
—, Schmidley JW, Fishmann RA, Longar SM (1984) Brain injury, edema, and vascular permeability changes induced by oxygen derived free radicals. Neurology (Cleveland) 34: 315–320
Csanda E (1980) Radiation brain edema. Adv Neurol 28: 325–346
Cummings JN (1961) Soluble cerebral proteins in normal and oedematous brain. J Clin Path 14: 289–295
Durward Q, Del Maestro RF, Amacher L, Farrer JK (1983) The influence of systemic arterial pressure and ICP on the development of cerebral vasogenic edema. J Neurosurg 59: 803–809
Ebner A, Einsiedel-Lechtape H, Luking CH (1982) Somatosensory tibial nerve evoked potentials with parasagital tumours: a contribution to the problem of generators. Electroencephalogs Clin Neurophysiol 54: 508–515
Fehlings D, Tator C, Linden R, Piper IR (1988) Motor and somatosensory evoked potentials recorded from the rat. Electroencephalogs Clin Neurophysiol 69: 65–78
Feigin I, Popoff N (1963) Neurpathological observations on cerebral oedema. Arch Neurol 6: 151–160
Fishmann RA (1976) Brain edema. N Engl J Med 293: 705–711
Galicich JH, French LA, Melby JC (1961) Use of dexamethasone in the treatment of cerebral edema associated with brain tumours. Lancet 81: 46–53
Greenfield JG (1939) The histology of cerebral oedema associated with intracranial tumours. Brain 62: 129–152
Hall RD, Lindholm EP (1974) Organization of motor and somatosensory neocortex in the albino rat. Brain Res 66: 23–38
Hatam A, Bergstrom M, Yu ZY, Granholm L, Berggren BM (1983) Effects of dexamethasone treatment on volume and contrast enhancement of intracranial neoplasms. J Comput Assist Tomogr 7: 295–300
Hatashita S, Hoff JT (1988) Biomechanics of brain edema in acute cerebral ischemia in the cat. Stroke 19: 91–97
Hillered L, Chan PH (1988) Effects of arachidonic acid on respiratory activities in isolated brain. J Neurol Sco 19: 94–100
Hossman KA, Bloink M, Wilmes F, Wechsler W (1980) Experimental peritumoural edema of cat brain. Adv Neurol 28: 323–340
Kingman TA, Mendelow AD, Graham DI, Teasdale GM (1988) Experimental intracranial mass lesion. Description of model, intracranial pressure changes and neuropathology. J Neuropathol Exp Neurol 47: 128–137
Klatzo I (1967) Presidential address. Neuropathological aspects of brain edema. J Neuropathol Exp Neurol 26: 1–14
Krieg WJ (1946) Connections of the cerebral cortex. I The albino rat. A. Topography of the cortical areas. B. Structure of the cortical areas. J Comp Neurol 84: 222–323
Lauritzen M (1984) Long lasting reduction of cortical blood flow in the rat brain after spreading depression and impaired CO2 response. J CBF Metab 4: 546–554
Lax F, Horoupian DS, Tagaki H, Marmarou A (1979) Microvascular changes in infusion edema. J Neuropathol Exp Neurol 38: 328
Lerch KD, von Wild K (1983) Influence of alpha methyl prednisolone on perifocal brain edema: CT observations in ten patients with circumscribed supratentorial brain tumours. Neurochirurgia (Stuttg) 26: 97–103
McKenzie ET, Scatton B (1987) Cerebral circulatory and metabolic effects of perivascular neurotransmitters. CRC Crit Rev Clin Neurobiol 2: 357–419
Marmarou A, Takagi H, Shulman K (1980) Biomechanics of brain edema and effects on local blood flow. Adv Neurol 28: 345–358
Marmarou A, Tanaka K, Shulman K (1982) An improved gravimetric measure of cerebral edema. J Neurosurg 56: 246–253
Miller JD (1979) The management of cerebral oedema. Br J Hosp Med 21: 152–165
—, Sakalas R, Ward JD (1977) Methylprednisolone treatment of patients with brain tumours. Neurosurgery 1: 114–119
Mosmans PCM (1974) Regional cerebral blood flow in neurological patients. Van Gorcum & Co, Assen, Netherlands, pp 62–71
Nakagawa H, Groothuis D, Owens ES, Fenstermacher JD, Patlak CS, Balsberg RG (1987) Dexamethasone effects in [125I] albumin distribution in experimental RG-2 gliomas and adjacent brain. J CBF Metab 7: 687–701
Pasztor E, Symon L, Dorsch NWC, Branston NM (1973) The hydrogen clearance method in assessment of blood flow in cortex, white matter and deep nuclei of baboons. Stroke 4: 556–567
Palvolgyi R (1969) Regional cerebral blood flow in patients with intracranial tumours. J Neurosurg 31: 149–163
Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Acad Press, Sydney.
Penn RD (1980) Cerebral edema and neurological function in human beings. Neurosurgery 6: 249–254
Reilly PL, Farrar JK, Miller JD (1977) Vascular reactivity in the primate brain after acute cryogenic injury. J Neurol Neurosurg Psychiat 40: 1092–1101
Ryan B, Joiner BL, Ryan TA (1985) MINITAB. Duxbury Press, Boston, Mass, pp 379
Schaul N, Ball K, Gloor P, Pappius H (1976) The EEG in cerebral edema. In: Pappius H, Feindel M (eds) Dynamics of brain edema. Springer, Berlin Heidelberg New York, pp 144–149
Scheinker IM (1947) Histopathology, classification and clinical significance of brain oedema. J Neurosurg 4: 255–275
Seitz RJ, Wechsler W (1987) Immunohistochemical demonstration of serum proteins in human cerebral gliomas. Acta Neuropath (Berl) 73: 145–152
Stohr M, Dichgans SJ, Voigt K, Buttner W (1983) The significance of somatosensory evoked potentials for localization of unilateral lesions within the cerebral hemispheres. J Neurol Sci 61: 49–63
Sutton LN, Bruce DA, Welsh FA, Jaggi JL (1980) Metabolic and electrophysiological consequences of vasogenic brain edema. Adv Neurol 28: 241–254
Szymas J, Hossmann KA (1984) Immunofluorescent investigation of extravasated serum proteins in human brain tumour and adjacent structures. Acta Neurochir (Wien) 17: 229–241
Tanaka K, Marmarou A, Nishimura S (1983) Electrophysiological and regional cerebral blood flow changes associated with direct infusion edema. In: Ishii S, Nagai H, Brock M (eds) Intracranial pressure V, Springer, Berlin Heidelberg New York, pp 413–418
Tsubokawa T, Doi N, Ohata H, Kondo T (1983) The effects of brain edema fluid on cerebral blood flow in tissue infusion model. In: Ishii S, Nagai H, Brock M (eds) Intracranial pressure V. Springer, Berlin Heidelberg New York, pp 419–423
Wahl M, Unterberg A, Baethmann A (1988) Mediators of blood brain barrier dysfunction and formation of vasogenic brain oedema. J CBF Metab 8: 621–634
Walstra G, Takagi H, Marmarou A, Shapiro K, Schulman K (1980) The time course of brain tissue compliance and resistance in a controlled model of brain oedema. In: Schulman K, Marmarou A, Miller JD, Becker D, Hochwald G, Brock M (eds) Intracranial pressure IV. Springer, Berlin Heidelberg New York, pp 253–256
Whittle IR (1989) The contribution of secondary mediators to the etiology and pathophysiology of brain oedema: Experimental studies using an infusion model. PhD Thesis, University of Edingburgh, pp 186
Wiederholt WG, Iragui-Madoz VJ (1977) Far field somatosensory potentials in the rat. EEG Clin Neurophysiol 42: 456–465
Yamada K, Bremer AM, West CR (1979) Effects of dexamethasone on tumor induced brain oedema and its distribution in the monkey. J. Neurosurg. 50: 361–367.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Whittle, I.R., Miller, J.D. A rodent model of infusion brain edema: Methodology and pathophysiological effects of saline and protein infusions. Acta neurochir 105, 158–168 (1990). https://doi.org/10.1007/BF01670001
Issue Date:
DOI: https://doi.org/10.1007/BF01670001