Isolated brain

Isolated brain

Isolated brain refers to keeping a brain alive in-vitro. This is done either by perfusion by a blood substitute, often an oxygenated solution of various salts, or by submerging the brain in oxygenated artificial cerebrospinal fluid (Bohlen, Halbach). It is the biological counterpart of brain in a vat. A related concept, attaching the brain or head to the circulatory system of another organism, is called a head transplant. An isolated brain however is more typically attached to an artificial perfusion device rather than a biological body.

The brains of many different organisms have been kept alive in-vitro for hours, or in some cases days. The central nervous system of invertebrate animals is often easily maintained as they need less oxygen and to a larger extent get their oxygen from CSF, for this reason the brains are more easily maintained without perfusion (Luksch, Walkowiak). Mammalian brains on the other hand have a much lesser degree of survival without perfusion and an artificial blood perfusate is usually used.

Most research on isolating mammalian brains has been done on guinea pigs.


*1812 - Julien Jean César Le Gallois (a.k.a. Legallois) put forth the original idea for resuscitating decapitated heads through the use of blood transfusion. [ [ Google Scholar:("Le Gallois" OR Legallois) 1812] ]
*1836 - Cooper showed in rabbits that compression of the carotid and vertebral arteries leads to death of an animal; such deaths can be prevented if the circulation of oxygenated blood to the brain is rapidly restored.
*1857 - Brown-Sequard decapitated a dog, waited ten minutes, attached four rubber tubes to the arterial trunks of the head, and injected blood containing oxygen by means of a syringe. Two or three minutes later voluntary movements of the eyes and muscles of the muzzle resumed. After cessation of oxygenated blood transfusion movements stopped.
*1887 - Laborde made what appears to be first recorded attempt to revive the heads of executed criminals by connecting the carotid artery of the severed human head to the carotid artery of a large dog. According to Laborde's account, in isolated experiments a partial restoration of brain function was attained.
*1912 - Heymans maintained life in an isolated dog's head by connecting the carotid artery and jugular vein of the severed head to the carotid artery and jugular vein of another dog. Partial functioning in the severed head was maintained for a few hours.
*1928 - Bryukhonenko and Cechulin showed life could be maintained in the severed head of a dog by connecting the carotid artery and jugular vein to an artificial circulation machine.
*1963 - Robert J. White isolated the brain from one monkey and attached it to the circulatory system of another animal.

Isolated brains in fiction

The concept of a brain in a jar is a common theme in science fiction. In the animated series "Futurama", numerous technological advances have been made by the 31st century. The ability to keep heads alive in jars was invented by Ron Popeil (who has a guest cameo in "A Big Piece of Garbage"), and has resulted in many political figures and celebrities being active; this became the writers' excuse to feature and poke fun at celebrities in the show.

The Mi-go aliens in the in Cthulhu Mythos can transport humans from Earth to Pluto (and beyond) and back again by removing the subject's brain and placing it into a "brain cylinder", which can be attached to external devices to allow it to see, hear, and speak.

Brain in a vat in philosophy

In philosophy, the brain in a vat is any of a variety of thought experiments intended to draw out certain features of our ideas about knowledge, reality, truth, mind, and meaning. A contemporary version of the argument originally given by Descartes in "Meditations on First Philosophy" (i.e., that he could not trust his perceptions on the grounds that an evil demon might, conceivably, be controlling his every experience), the "brain in a vat" is the idea that a brain can be fooled into anything when fed appropriate stimuli.

The inherently philosophical idea has also became a staple of many science fiction stories, with many such stories involving a mad scientist who might remove a person's brain from the body, suspend it in a vat of life-sustaining liquid, and connect its neurons by wires to a supercomputer which would provide it with electrical impulses identical to those the brain normally receives. According to such science fiction stories, the computer would then be simulating a virtual reality (including appropriate responses to the brain's own output) and the person with the "disembodied" brain would continue to have perfectly normal conscious experiences without these being related to objects or events in the real world.

Growing an isolated brain

An isolated biological brain, grown from cultured neurons which were originally separated, has been developed as the neurological entity subsequently embodied within a robot body by Kevin Warwick and his team. The brain receives input from sensors on the robot body and the resultant output from the brain provides the robot's only motor signals. The biological brain is the only brain of the robot [ [] Xydas, D.,Norcott, D.,Warwick, K.,Whalley, B.,Nasuto, S.,Becerra, V.,Hammond, M.,Downes, J.and Marshall, S.,"Architecture for Neuronal Cell Control of a Mobile Robot", European Robotics Symposium 2008, Prague, March 2008, Springer.] .



*Librizzi L, Janigro D, De Biasi S, de Curtis M. Blood-brain barrier preservation in the in vitro isolated guinea pig brain preparation. J Neurosci Res. 2001 Oct 15;66(2):289-97. PMID 11592126
*Mazzetti S, Librizzi L, Frigerio S, de Curtis M, Vitellaro-Zuccarello L. Molecular anatomy of the cerebral microvessels in the isolated guinea-pig brain. Brain Res. 2004 Feb 27;999(1):81-90. PMID 14746924
*Mühlethaler M, de Curtis M, Walton K, Llinás R. The isolated and perfused brain of the guinea-pig in vitro. Eur J Neurosci. 1993 Jul 1;5(7):915-26. PMID 8281302
*Luksch H, Walkowiak W, Muñoz A, ten Donkelaar HJ. The use of in vitro preparations of the isolated amphibian central nervous system in neuroanatomy and electrophysiology. J Neurosci Methods. 1996 Dec;70(1):91-102. PMID 8982986
*von Bohlen and Halbach O. The isolated mammalian brain: an in vivo preparation suitable for pathway tracing. Eur J Neurosci. 1999 Mar;11(3):1096-100. PMID 10103102
*Kerkut GA. Studying the isolated central nervous system; a report on 35 years: more inquisitive than acquisitive. Comp Biochem Physiol A. 1989;93(1):9-24. Review. PMID 2472918
*Llinás R, Yarom Y, Sugimori M. Isolated mammalian brain in vitro: new technique for analysis of electrical activity of neuronal circuit function. Fed Proc. 1981 Jun;40(8):2240-5. PMID 7238908

Further reading

*Chute-AL, Smyth-DH. Metabolism of the isolated perfused cat's brain. Quart J Exp Physiol 29:379-394 (1939).
*Geiger-A, Magnes-J. The isolation of the cerebral circulation and the perfusion of the brain in the living cat. Am J Physiol 149:517-536 (1947).
*Geiger-A. Correlation of brain metabolism and function by use of a brain perfusion method in situ. Physiol Rev 38:1-20 (1958).
*Geiger-A. Technique of brain perfusion in situ. Methods Med Res 9:248-254 (1961).
*Demikhov-VP. Transplantation of the Head. "Experimental Transplantation of Vital Organs". Consultants Bureau, New York (1962).
*Meder-R, Massopust-LC-Jr, White-RJ, Verdura-J, Albin-MS. Isolated brain perfusion--electromechanical system requirements. Proc 16th Ann Conf Eng Med Biol 5:28-29 (1963).
*White-RJ, Albin-MS, Verdura-J. Isolation of the monkey brain: in vitro preparation and maintenance. Science 141:1060 (1963).
*Gilboe-DD, Cotanch-WW, Glover--MB. Extracorporeal perfusion of the isolated head of a dog. Nature 202:399-400 (1964).
*Sano-K, Terao-H, Hayakawa-I, Kamano-S, Saito-I. Experimental transplantation of the head: two-headed dogs. Neurol Medicochir (Tokoyo) 6:35-38 (1964).
*White-RJ, Albin-MS, Verdura-J. Preservation of viability in the isolated monkey brain utilizing a mechanical extracorporeal circulation. Nature (Lond) 202:1082-1083 (1964).
*Gilboe-DD, Cotanch-WW, Glover-MB. Isolation and mechanical maintenance of the dog brain. Nature (Lond.) 206:94-96 (1965).
*White-RJ, Albin-MS, Locke-GE, Davidson-E. Brain transplantation: prolonged survival of brain after carotid-jugular interposition. Science 150:779 (1965).
*White-RJ, Albin-MS, Locke-GE, Davidson-E. Transplantation of the isolated canine brain. Physiologist 8:304 (1965).
*Suda-I, Kito-K, Adachi-C. Viability of long term frozen cat brain in vitro. Nature 212:268 (1966).
*White-RJ, Albin-MS, Locke-GE. Vascular preparation of the isolated canine brain. Anatomical Record 154:441 (1966).
*White-RJ, Albin-MS, Locke-GE. Whole brain preservation near 0 degrees C. Cryobiology 2:315 (1966).
*White-RJ, Albin-MS, Verdura-J, Locke-GE. Prolonged whole brain refrigeration with electrical and metabolic recovery. Nature 209:1320 (1966).
*Allweis-C, Abeles-M, Magnes-J. Perfusion of cat brain with simplified blood after filtration through glass wool. Amer J Physiol 213:83-86 (1967).
*Andjus-RK, Suhara-S, Sloviter-HA. An isolated, perfused rat brain preparation, its spontaneous and stimulated activity. J Appl Physiol 22:1033-1039 (1967).
*Sloviter-HA, Kamimoto-T. Erythrocyte substitute for perfusion of brain. Nature (lond) 216:458-460 (1967).
*Taslitz-N, Acosta-Rua-G, White-RJ, Albin-MS. The rat brain as an isolated organ preparation. Anat Rec 157:332 (1967).
*White-RJ, Albin-MS, Verdura-J, Locke-GE. The isolated monkey brain: operative preparation and design of support systems. J Neurosurg 27:216-225 (1967).
*White-RJ, Albin-MS, Locke-GE, Davidson-E. Preparation and metabolic performance of the transplanted brain. Surgical Forum 18:463 (1967).
*White-RJ, Albin-S, Yashon-D, Austin-J, Austin-P, Taslitz-N. Mechanical circulatory support of the failing brain. Trans Amer Soc Artif Int Organ 14:349-351 (1968).
*White-RJ, Albin-MS. Mechanical circulatory support of the isolated brain. "Organ perfusion and preservation." (Norman-JC, Folkman-J, Hardison-WG, Rudolf-LE, Veith-FJ eds). Appleton-Century Crofts, NY. (1968).
*White-RJ. "Experimental transplantation of the brain." Human Transplantation (Rapaport-FT, Dausset-J eds). pp 692-709 (1968).
*Thompson-AM, Robertson-RC, Bauer-TA. A rat head-perfusion technique developed for the study of brain uptake of materials. J Appl Physiol 24:407-411 (1968).
*White-RJ, Albin-MS, Yashon-D. Neuropathological investigation of the transplanted canine brain. Transplant Proceed 1:259 (1969).
*Clark-LC, Kaplan-S, Becattini-F, Benzing-G. Perfusion of whole animals with perfluorinated liquid emulsions using the Clark bubble-defoam heart-lung machine. Fed Proc Am Soc Exp Biol 29:1764-1770 (1970).
*Taslitz-N, White-RJ, Wolin-LR, Yashon-D. Adequacy of single carotid perfusion of the brain. Anatomical Record 166:388 (1970).
*White-RJ, Albin-MS, Yashon-D, Verdura-J, Austin-JC, Austin-PE-Jr, Demian-YK. Autoregulation in the isolated brain during profound hypothermia and hypercarbia. Brain and Blood Flow (Ross-RW ed). Pitman, London. pp.209 (1970).
*Horst-WD, Jester-J. The use of isolated perfused rat brain in a study of 14-C-L-Dopa metabolism. Life Sci 10(I):685-689 (1971).
*Jahnchen-E, Krieglstein-J. Die aufnahme von promazin, chlorpromazin und deren desmethylmetaboliten in das isoliert perfundierte rattenhirn. Naunyn- Schmiedebergs Arch Pharmak 268:300-309 (1971).
*Mukherji-B, Turinsky-J, Sloviter-HA. Effects of perfusion without glucose on amino acids and glycogen of isolated rat brain. J Neurochem 18:1783-1785 (1971).
*Sloviter-HA, Yamada-H. Absence of direct action of insulin on metabolism of the isolated perfused rat brain. J Neurochem 18:1269-1274 (1971).
*White-RJ, Wolin-LR, Massopust-LC, Taslitz-N, Verdura-J. Primate cephalic transplantation: neurogenic separation, vascular association. Transplantation Proceedings 3:602-604 (1971).
*Vasan-NS, Abraham-J, Bachhawat-BK. Sulphate metabolism in acute EAE rats using isolated brain perfusion technique. J Neurochem 18:59-66 (1971).
*Zimmer-R, Lang-R, Oberdoister-G. Post-ischaemic reactive hyperaemia of the isolated perfused brain of dog. Pflugers Arch Ges Physiol 328:332-343 (1971).
*Fleck-WV, Krieglstein-J, Urban-W. Zwei apparaturen zur perfusion des isolierten rattenhirns. Arzneim-Forsch 22:1225-1230 (1972).
*Ghosh-AK, Mukherji-B, Slovitar-HA. Metabolism of isolated rat brain perfused with glucose or mannose as substrate. J Neurochem 19:1279-1285 (1972).
*Krieglstein-G, Krieglstein-J, Stock-R. Suitability of the isolated perfused rat brain for studying effects on cerebral metabolism. Naunyn-Schmiedeberg's Arch Pharmacol 275:124-134 (1972).
*Krieglstein-G, Krieglstein-J, Urban-W. Long survival time of an isolated perfused rat brain (Short Communication). J Neurochem 19:885-886 (1972).
*Stock-R, Krieglstein-G, Krieglstein-J. Studies on energy metabolism of an isolated perfused rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 274:R112 (1972).
*Zivin-JA, Snarr-JF. A stable preparation for rat brain perfusion: effect of flow rate on glucose uptake. J Appl Physiol 32:658-663 (1972).
*Zivin-JA, Snarr-JF. Glucose and D(-)-3-hydroxybutyrate uptake by isolated perfused rat brain. J Appl Physiol 32:664-668 (1972).
*Fleck-W, Krieglstein-J, Reichmann-M. A two-circuit apparatus for the perfusion of the isolated rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 278:319-322 (1973).
*Gruner-J, Krieglstein-J, Rieger-H. Comparison of the effects of chloral hydrate and trichloroethanol on the EEG of the isolated perfused rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 277:333-348 (1973).
*Krieglstein-J, Stock-R. Comparative study of the effects of chloral hydrate and trichloroethanol on cerebral metabolism. Naunyn-Schmiedeberg's Arch Pharmacol 277:323-332 (1973).
*Krieglstein-J, Stock-R, Rieger-H. Influence of therapeutic and toxic doses of neuroleptics and antidepressants on energy metabolism of the isolated perfused rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 279:243-254 (1973).
*Krieglstein-J, Stock-R. The isolated perfused rat brain as a model for studying drugs acting on the CNS. Psychopharmacologia 35:169-177 (1974).
*White-RJ. Hypothermic preservation and transplantation of brain. Resuscitation 4:197 (1975).
*Woods-HF, Graham-CW, Green-AR, Youdim-MBH, Grahame-Smith-DG, Highes-JT. Some histological and metabolic properties of an isolated perfused rat brain preparation with special reference to monoamine metabolism. Neuroscience 1:313-323 (1976).
*Woods-HF, Youdim-MBH. The isolated perfused rat brain preparation--a critical assessment. Essays Neurochem Neuropharmacol 3:49-69 (1978).
*Dirks-B, Krieglstein-J, Lind-HH, Rieger-H, Schutz-H. Fluorocarbon perfusion medium applied to the isolated rat brain. J Pharm Methods 4:95-108 (1980).
*Llinas-R, Yarom-Y, Sugimori-M. Isolated mammalian brain in vitro: new technique for analysis of electrical activity of neuronal circuit function. Fed Proc 40(8)-2240-2245 (1981).
*Shapovalov-AI, Shiriaev-BI, Tamarova-ZA. "A study of neuronal activity of mammalian superfused or intra-arterially perfused CNS preparations." Electrophysiology of isolated mammalian CNS preparations (Kerkut-GA, Wheal-HV eds). pp 367-394 (1981).

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