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A simplified intracranial cannula for chemical stimulation or long-term infusion of the brain
I'hysiology and Behavior. Vol. 2. pp. 87-88. Pelllmon Preu Ltd.. 1967 Printed in Great Britain
BRIEF COMMUNICATION A Simplified Intracranial Cannula for Chemical Stimulation' or Long-term Infusion of the Brain R O B E R T D. MYERS, G E O R G E
CASADAY
A N D R. B R U C E H O L M A N
Purdue University, Lafayette, Indiana (Received 15 July 1966) MYERS. R. D., G. CASADAYAND R. B. HOLMAN. A simplified intracranial cannula for chemical stimulation or long-term infusion of the brain. PHYSIOL.BEHAV. 2 (1) 87-88, 1967.--A small, easily constructed, lightweight cannula assembly is
described for chronic or acute intracerebral injections of solutions into small animals. Stainless steel injector and guide cannulae are fitted to the plastic cap and Luer end of a disposable tuberculin syringe. Details of fabrication and usage are presented. Cerebral cannula
Brain injections
Cerebral ventricular injection
SEVERAL METHODS HAVE been utilized for the administration of drugs and chemicals to specific sites [2, 4, 6, 8] or regions [1] within the central nervous system. In each case a cannula or tubing system permits the direct application of a substance either in solution or in crystalline form. Several years ago a system was devised for chronic injection of chemical solutions
Chemical stimulation of brain
into the ventricular system [5] and then adapted for direct injection into cerebral tissue [3, 7]. An improved cannula, which has the distinct advantages of small size, light weight, and ease of construction is described here for use with small animals. Stainless steel 22 gauge hypoflex tubing (Superior Tube Co.,
A STILETTE~ BIRACO TUBING
CAP-.~I_~
INJECTOR CANNULA 0
CRANIO PLAST gmxY
~.,..C~IDE CANNULA
NTRICLE
FIG. 1 A (left). Base with the guide carmula cemented in place. Stiletta which is affixed to the cap before implantation is shown partially lowered within the guide cannula. 1 B (r/A,ht). Guide cannula-base assembly after implantation into the lateral ventricle of a rat. Tip of the injector cannula rests in the ventricle. Other end is attached to PE-10 tubing which is threaded through and taped to protective Biraco tubing. Cannula base is fixed to the cranium miniature screws and cranioplast. 1This research was supported in part by National Science Foundation Grant GB 3874 and by a grant from Wallace Laboratories. We are indebted to Peter F. East, Head Technician of the Laboratory of Neuropsychology for his advice and aid in this research.
87
88
MYERS, CASADAY AND ItOLMAN
Norristown, Pa.) used for the outer or guide cannula is cemented with Araldite epoxyresin glue (Ciba Ltd., Cambridge, England) into a plastic base cut from the needle end of a 1 ml disposable tuberculin syringe (Becton-Dickinson Co., Rutherford, N . J . ) . After the base is cut away from the syringe, its dia is 7 mm and over-aU height is 11 mm. The length of the guide cannula is dictated by the specific cerebral structure or ventricular area in which an injection is to be made. F o r instance, when used for intraventricular injections in rats, the outer cannula is cemented so that its tip extends 6 mm beyond the plastic base and will rest between 4 and 5 mm below the level of the dura mater after implantation. The end of the cannula is beveled at an angle of 30 degrees to provide maximum access for fluids injected into the ventricular lumen. Figure 1 A illustrates the guide cannula base assembly A plastic cap, which comes on the end of each disposable syringe, is employed as a protective cover for the cannula after it is implanted into the animal. The cannula base is threaded with a 3/16 in. die and the cap with a 3/16 in. tap. With a 28 gauge stilette inserted through and cemented to the cap, the opening of the cannula is maintained and the loss of cerebrospinal fluid is prevented if the tip of the cannula lies in the lateral or third ventricle. The inner or injector cannula consists of a length of 28 gauge stainless steel tubing, which is inserted through a hole drilled vertically in the center of another plastic syringe cap. Araldite cement is then applied to the outside of the cap and the injector cannula fixed in place. The injector cannula is cut to such a length that when the cap is screwed down t i g h t l y on the cannula base, the tip of the injector cannula rests in the middle of the bevel. This is shown in Fig. 1 B for
an injection to be made into the cerebral ventricle. Polyethylene tubing PE-10 (Clay Adams, New York), is fastened by friction fit to the tip of this cannula and subsequently attached either to a micro-injection syringe for single injections o f a drug [7] or to a micro-infusion pump system for repeated and remotely programmed infusions [5]. For maintaining chronic preparations, a 4 cm length of polyvinyl tubing (Biraco 318-B size 8, Birnbach Radio Co., New York) is attached to the top of the cap. The PE-10 tubing is then threaded through a 3 mm hole cut in the upper and posterior part of the tubing so that the PE-10 is protected during sleep and beyond the animal's grasp during grooming. Adhesive tape is wrapped around the opening in the Biraco tubing to keep the PE-10 in place. Figure I B shows the outer cannula-base assembly, with the PE-10 tubing and injector cannula in position for an infusion. The dimensions of the cap are 12 mm in height and 9 mm in dia and the overall height of the cannula base plus cap is 16 mm. The weight of the entire cannula assembly is 0.76 g as compared to 2.95 g for a similar cannula [5] made from a stainless steel syringe needle. Stereotaxic implantation as well as the fixation of the cannula base to the cranium are carried out by means of screws and cranioplast cement according to standard procedures. Since the materials in the plastic base and cannulae are not tissue reactive, the cannula assembly may be used for implantations designed to endure over extended periods of time. Rats which have been implanted with this cannula assembly have survived for several months and have been used repeatedly for a number of infusions or stimulations.
REFERENCES
I. Carmichael, E., W. Feldberg and K. Fleischhauer. Methods for peffusing different parts of the cat's cerebral ventricles with drugs. J. Physiol. (Lond.) 173: 354--367, 1964. 2. Endroczi, E., G. Hartmann and K. Lissak. Effect of intracerebrally administered cholinergic and adrenergic drugs on neocortical and archicortical electrical activity. Acta Physiol. Hung. 24: 199-209, 1963. 3. Feldberg, W. and R. D. Myers. Changes in temperature produced by microinjections of amines into the anterior hypothalamus of cats. J. Physiol. (Lond.) 177: 239-245, 1965. 4. MacLean, P. D. Chemical and electrical stimulation of hippocampus in unrestrained animals. 1. Methods and electroencephalographic findings. A.M.A. Archs Neuro[. Psychiatry 78: 113-127, 1957.
5. Myers, R. D. An intracranial chemical stimulation system for chronic or self-infusion. J. Appl. Physiol. 18: 221-223, 1963. Myers, R. D. Injection of solutions in cerebral tissue: relation between volume and diffusion. Physiol. Behav. 1: 171-174, 1966. Myers, R. D. Emotional and autonomic responses following hypothalamic chemical stimulation. Can. J. Psychol. 18: 6-14, 1964. Nashold, B. and J. Gills. Chemical stimulation of telencephalon, dieneephalon and mesencephalon in unrestrained animals. J. Neuropathol. Exp. Neurol. 19: 580-590, 1960.
BRIEF COMMUNICATION A Simplified Intracranial Cannula for Chemical Stimulation' or Long-term Infusion of the Brain R O B E R T D. MYERS, G E O R G E
CASADAY
A N D R. B R U C E H O L M A N
Purdue University, Lafayette, Indiana (Received 15 July 1966) MYERS. R. D., G. CASADAYAND R. B. HOLMAN. A simplified intracranial cannula for chemical stimulation or long-term infusion of the brain. PHYSIOL.BEHAV. 2 (1) 87-88, 1967.--A small, easily constructed, lightweight cannula assembly is
described for chronic or acute intracerebral injections of solutions into small animals. Stainless steel injector and guide cannulae are fitted to the plastic cap and Luer end of a disposable tuberculin syringe. Details of fabrication and usage are presented. Cerebral cannula
Brain injections
Cerebral ventricular injection
SEVERAL METHODS HAVE been utilized for the administration of drugs and chemicals to specific sites [2, 4, 6, 8] or regions [1] within the central nervous system. In each case a cannula or tubing system permits the direct application of a substance either in solution or in crystalline form. Several years ago a system was devised for chronic injection of chemical solutions
Chemical stimulation of brain
into the ventricular system [5] and then adapted for direct injection into cerebral tissue [3, 7]. An improved cannula, which has the distinct advantages of small size, light weight, and ease of construction is described here for use with small animals. Stainless steel 22 gauge hypoflex tubing (Superior Tube Co.,
A STILETTE~ BIRACO TUBING
CAP-.~I_~
INJECTOR CANNULA 0
CRANIO PLAST gmxY
~.,..C~IDE CANNULA
NTRICLE
FIG. 1 A (left). Base with the guide carmula cemented in place. Stiletta which is affixed to the cap before implantation is shown partially lowered within the guide cannula. 1 B (r/A,ht). Guide cannula-base assembly after implantation into the lateral ventricle of a rat. Tip of the injector cannula rests in the ventricle. Other end is attached to PE-10 tubing which is threaded through and taped to protective Biraco tubing. Cannula base is fixed to the cranium miniature screws and cranioplast. 1This research was supported in part by National Science Foundation Grant GB 3874 and by a grant from Wallace Laboratories. We are indebted to Peter F. East, Head Technician of the Laboratory of Neuropsychology for his advice and aid in this research.
87
88
MYERS, CASADAY AND ItOLMAN
Norristown, Pa.) used for the outer or guide cannula is cemented with Araldite epoxyresin glue (Ciba Ltd., Cambridge, England) into a plastic base cut from the needle end of a 1 ml disposable tuberculin syringe (Becton-Dickinson Co., Rutherford, N . J . ) . After the base is cut away from the syringe, its dia is 7 mm and over-aU height is 11 mm. The length of the guide cannula is dictated by the specific cerebral structure or ventricular area in which an injection is to be made. F o r instance, when used for intraventricular injections in rats, the outer cannula is cemented so that its tip extends 6 mm beyond the plastic base and will rest between 4 and 5 mm below the level of the dura mater after implantation. The end of the cannula is beveled at an angle of 30 degrees to provide maximum access for fluids injected into the ventricular lumen. Figure 1 A illustrates the guide cannula base assembly A plastic cap, which comes on the end of each disposable syringe, is employed as a protective cover for the cannula after it is implanted into the animal. The cannula base is threaded with a 3/16 in. die and the cap with a 3/16 in. tap. With a 28 gauge stilette inserted through and cemented to the cap, the opening of the cannula is maintained and the loss of cerebrospinal fluid is prevented if the tip of the cannula lies in the lateral or third ventricle. The inner or injector cannula consists of a length of 28 gauge stainless steel tubing, which is inserted through a hole drilled vertically in the center of another plastic syringe cap. Araldite cement is then applied to the outside of the cap and the injector cannula fixed in place. The injector cannula is cut to such a length that when the cap is screwed down t i g h t l y on the cannula base, the tip of the injector cannula rests in the middle of the bevel. This is shown in Fig. 1 B for
an injection to be made into the cerebral ventricle. Polyethylene tubing PE-10 (Clay Adams, New York), is fastened by friction fit to the tip of this cannula and subsequently attached either to a micro-injection syringe for single injections o f a drug [7] or to a micro-infusion pump system for repeated and remotely programmed infusions [5]. For maintaining chronic preparations, a 4 cm length of polyvinyl tubing (Biraco 318-B size 8, Birnbach Radio Co., New York) is attached to the top of the cap. The PE-10 tubing is then threaded through a 3 mm hole cut in the upper and posterior part of the tubing so that the PE-10 is protected during sleep and beyond the animal's grasp during grooming. Adhesive tape is wrapped around the opening in the Biraco tubing to keep the PE-10 in place. Figure I B shows the outer cannula-base assembly, with the PE-10 tubing and injector cannula in position for an infusion. The dimensions of the cap are 12 mm in height and 9 mm in dia and the overall height of the cannula base plus cap is 16 mm. The weight of the entire cannula assembly is 0.76 g as compared to 2.95 g for a similar cannula [5] made from a stainless steel syringe needle. Stereotaxic implantation as well as the fixation of the cannula base to the cranium are carried out by means of screws and cranioplast cement according to standard procedures. Since the materials in the plastic base and cannulae are not tissue reactive, the cannula assembly may be used for implantations designed to endure over extended periods of time. Rats which have been implanted with this cannula assembly have survived for several months and have been used repeatedly for a number of infusions or stimulations.
REFERENCES
I. Carmichael, E., W. Feldberg and K. Fleischhauer. Methods for peffusing different parts of the cat's cerebral ventricles with drugs. J. Physiol. (Lond.) 173: 354--367, 1964. 2. Endroczi, E., G. Hartmann and K. Lissak. Effect of intracerebrally administered cholinergic and adrenergic drugs on neocortical and archicortical electrical activity. Acta Physiol. Hung. 24: 199-209, 1963. 3. Feldberg, W. and R. D. Myers. Changes in temperature produced by microinjections of amines into the anterior hypothalamus of cats. J. Physiol. (Lond.) 177: 239-245, 1965. 4. MacLean, P. D. Chemical and electrical stimulation of hippocampus in unrestrained animals. 1. Methods and electroencephalographic findings. A.M.A. Archs Neuro[. Psychiatry 78: 113-127, 1957.
5. Myers, R. D. An intracranial chemical stimulation system for chronic or self-infusion. J. Appl. Physiol. 18: 221-223, 1963. Myers, R. D. Injection of solutions in cerebral tissue: relation between volume and diffusion. Physiol. Behav. 1: 171-174, 1966. Myers, R. D. Emotional and autonomic responses following hypothalamic chemical stimulation. Can. J. Psychol. 18: 6-14, 1964. Nashold, B. and J. Gills. Chemical stimulation of telencephalon, dieneephalon and mesencephalon in unrestrained animals. J. Neuropathol. Exp. Neurol. 19: 580-590, 1960.