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Keith A. Crutcher

Volunteer Professor

Neurosurgery | College of Medicine

Contact Information
Research Interests

Crutcher Lab Research Program: The research program is focused on two major areas. The first is the study of themechanisms underlying axonal sprouting and abortive regeneration in the mature mammalian brain. The primary model involves studies of axonal sprouting in the CNS or on sections of the CNS. Some of the findings that have emerged from this research programin...

Peer Reviewed Publications

Pettigrew, David B; Singh, Niharika; Kirthivasan, Sabarish; Crutcher, Keith A 2022. The Role of Tissue Geometry in Spinal Cord Regeneration. Medicina (Kaunas, Lithuania), 58 4,

Pettigrew, David B; Dobson, Curtis B; Isaacson, Lori G; Leuthardt, Eric C; Lilley, Heather N; Suidan, Georgette L; Crutcher, Keith A 2019. Segregated neural explants exhibit co-oriented, asymmetric, neurite outgrowth. PloS one, 14 9, e0216263

Crutcher, K A; Lilley, H N; Anthony, S R; Zhou, W; Narayanaswami, V 2010. Full-length apolipoprotein E protects against the neurotoxicity of an apoE-related peptide. Brain research, 1306 , 106-15

Richeri, Analía; Bianchimano, Paola; Crutcher, Keith A; Brauer, M Mónica 2010. Reduced sympathetic neurite outgrowth on uterine tissue sections from rats treated with estrogen. Cell and tissue research, 340 2, 287-301

Shelton, Shirley B; Pettigrew, David B; Hermann, Alison D; Zhou, Weidong; Sullivan, Patrick M; Crutcher, Keith A; Strauss, Kenneth I 2008. A simple, efficient tool for assessment of mice after unilateral cortex injury. Journal of neuroscience methods, 168 2, 431-42

Zhou, Weidong; Xu, Di; Peng, Xiaoxia; Zhang, Qiuhong; Jia, Jianping; Crutcher, Keith A 2008. Meta-analysis of APOE4 allele and outcome after traumatic brain injury. Journal of neurotrauma, 25 4, 279-90

Pettigrew, David B; Li, Ya-Qin; Kuntz, Charles; Crutcher, Keith A 2007. Global expression of NGF promotes sympathetic axonal growth in CNS white matter but does not alter its parallel orientation. Experimental neurology, 203 1, 95-109

Crutcher, Keith A; Gendelman, Howard E; Kipnis, Jonathan; Perez-Polo, J Regino; Perry, V H; Popovich, Phillip G; Weaver, Lynne C 2006. Debate: "is increasing neuroinflammation beneficial for neural repair?". Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 1 3, 195-211

Dhanoa, Navnish K; Krol, Karmen M; Jahed, Ali; Crutcher, Keith A; Kawaja, Michael D 2006. Null mutations for exon III and exon IV of the p75 neurotrophin receptor gene enhance sympathetic sprouting in response to elevated levels of nerve growth factor in transgenic mice. Experimental neurology, 198 2, 416-26

Dobson, Curtis B; Sales, Sean D; Hoggard, Patrick; Wozniak, Matthew A; Crutcher, Keith A 2006. The receptor-binding region of human apolipoprotein E has direct anti-infective activity. The Journal of infectious diseases, 193 3, 442-50

Zhou, W; Scott, S A; Shelton, S B; Crutcher, K A 2006. Cathepsin D-mediated proteolysis of apolipoprotein E: possible role in Alzheimer's disease. Neuroscience, 143 3, 689-701

Crutcher, Keith A 2004. Apolipoprotein E is a prime suspect, not just an accomplice, in Alzheimer's disease. Journal of molecular neuroscience : MN, 23 3, 181-8

Marques, Marcos A; Owens, Phillip A; Crutcher, Keith A 2004. Progress toward identification of protease activity involved in proteolysis of apolipoprotein e in human brain. Journal of molecular neuroscience : MN, 24 1, 73-80

Cowen, T; Woodhoo, A; Sullivan, C D; Jolly, R; Crutcher, K A; Wyatt, S; Michael, G J; Orike, N; Gatzinsky, K; Thrasivoulou, C 2003. Reduced age-related plasticity of neurotrophin receptor expression in selected sympathetic neurons of the rat. Aging cell, 2 1, 59-69

Marques, Marcos A; Crutcher, Keith A 2003. Apolipoprotein E-related neurotoxicity as a therapeutic target for Alzheimer's disease. Journal of molecular neuroscience : MN, 20 3, 327-37

Qiu, Z; Crutcher, K A; Hyman, B T; Rebeck, G W 2003. ApoE isoforms affect neuronal N-methyl-D-aspartate calcium responses and toxicity via receptor-mediated processes. Neuroscience, 122 2, 291-303

Bazin, Hélène G; Marques, Marcos A; Owens, Albert P; Linhardt, Robert J; Crutcher, Keith A 2002. Inhibition of apolipoprotein E-related neurotoxicity by glycosaminoglycans and their oligosaccharides. Biochemistry, 41 25, 8203-11

Crutcher, Keith A 2002. Aging and neuronal plasticity: lessons from a model. Autonomic neuroscience : basic & clinical, 96 1, 25-32

Kudwa, A E; Shoemaker, S E; Crutcher, K A; Isaacson, L G 2002. Evidence for reduced accumulation of exogenous neurotrophin by aged sympathetic neurons. Brain research, 948 1-2, 24-32

Teter, Bruce; Raber, Jacob; Nathan, Britto; Crutcher, Keith A 2002. The presence of apoE4, not the absence of apoE3, contributes to AD pathology. Journal of Alzheimer's disease : JAD, 4 3, 155-63

Pettigrew, D B; Crutcher, K A 2001. Myelin contributes to the parallel orientation of axonal growth on white matter in vitro. BMC neuroscience, 2 , 9

Pettigrew, D B; Shockley, K P; Crutcher, K A 2001. Disruption of spinal cord white matter and sciatic nerve geometry inhibits axonal growth in vitro in the absence of glial scarring. BMC neuroscience, 2 , 8

Brauer, M M; Shockley, K P; Chávez, R; Richeri, A; Cowen, T; Crutcher, K A 2000. The role of NGF in pregnancy-induced degeneration and regeneration of sympathetic nerves in the guinea pig uterus. Journal of the autonomic nervous system, 79 1, 19-27

Krol, K M; Crutcher, K A; Kalisch, B E; Rylett, R J; Kawaja, M D 2000. Absence of p75(NTR) expression reduces nerve growth factor immunolocalization in cholinergic septal neurons. The Journal of comparative neurology, 427 1, 54-66

Shafer, A J; Crutcher, K A; Isaacson, L G 2000. Remodeling of adult sensory axons in the superior cervical ganglion in response to exogenous nerve growth factor. Brain research, 864 2, 252-62

Pettigrew, D B; Crutcher, K A 1999. White matter of the CNS supports or inhibits neurite outgrowth in vitro depending on geometry. The Journal of neuroscience : the official journal of the Society for Neuroscience, 19 19, 8358-66

Tolar, M; Keller, J N; Chan, S; Mattson, M P; Marques, M A; Crutcher, K A 1999. Truncated apolipoprotein E (ApoE) causes increased intracellular calcium and may mediate ApoE neurotoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience, 19 16, 7100-10

Walsh, G S; Krol, K M; Crutcher, K A; Kawaja, M D 1999. Enhanced neurotrophin-induced axon growth in myelinated portions of the CNS in mice lacking the p75 neurotrophin receptor. The Journal of neuroscience : the official journal of the Society for Neuroscience, 19 10, 4155-68

Joshi, S N; Crutcher, K A 1998. Rat microglia exhibit increased density on Alzheimer's plaques in vitro. Experimental neurology, 149 1, 42-50

Tolar, M; Scott, S A; Crutcher, K A 1998. Sympathetic neurite outgrowth is greater on plaque-poor vs. plaque-rich regions of Alzheimer's disease cryostat sections. Brain research, 787 1, 49-58

Kawaja, M D; Crutcher, K A 1997. Sympathetic axons invade the brains of mice overexpressing nerve growth factor. The Journal of comparative neurology, 383 1, 60-72

Tolar, M; Marques, M A; Harmony, J A; Crutcher, K A 1997. Neurotoxicity of the 22 kDa thrombin-cleavage fragment of apolipoprotein E and related synthetic peptides is receptor-mediated. The Journal of neuroscience : the official journal of the Society for Neuroscience, 17 15, 5678-86

Cowen, T; Gavazzi, I; Weingartner, J; Crutcher, K A 1996. Levels of NGF protein do not correlate with changes in innervation of the rat iris in old age. Neuroreport, 7 13, 2216-20

Fahnestock, M; Scott, S A; Jetté, N; Weingartner, J A; Crutcher, K A 1996. Nerve growth factor mRNA and protein levels measured in the same tissue from normal and Alzheimer's disease parietal cortex. Brain research. Molecular brain research, 42 1, 175-8

Isaacson, L G; Schwenk, K L; Billieu, S C; Crutcher, K A 1996. Sympathetic response to intracranial NGF infusion in the absence of afferent input: axonal sprouting without neurotransmitter production. Experimental neurology, 141 1, 57-66

Marques, M A; Tolar, M; Harmony, J A; Crutcher, K A 1996. A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific neurotoxicity. Neuroreport, 7 15-17, 2529-32

Tian, X; Scott, S A; Weingartner, J; Crutcher, K A 1996. Enhanced sympathetic neurite outgrowth on rat hippocampal tissue sections following septal lesions. Brain research, 725 1, 111-4

Isaacson, L G; Crutcher, K A 1995. The duration of sprouted cerebrovascular axons following intracranial infusion of nerve growth factor. Experimental neurology, 131 2, 174-9

Isaacson, L G; Ondris, D; Crutcher, K A 1995. Plasticity of mature sensory cerebrovascular axons following intracranial infusion of nerve growth factor. The Journal of comparative neurology, 361 3, 451-60

Scott, S A; Mufson, E J; Weingartner, J A; Skau, K A; Crutcher, K A 1995. Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis. The Journal of neuroscience : the official journal of the Society for Neuroscience, 15 9, 6213-21

Yu, C; Crutcher, K A 1995. Nerve growth factor immunoreactivity and sympathetic sprouting in the rat hippocampal formation. Brain research, 672 1-2, 55-67

Crutcher, K A; Clay, M A; Scott, S A; Tian, X; Tolar, M; Harmony, J A 1994. Neurite degeneration elicited by apolipoprotein E peptides. Experimental neurology, 130 1, 120-6

Crutcher, K A 1993. Tissue sections as culture substrates: overview and critique. Hippocampus, 3 Spec No , 157-63

Crutcher, K A; Anderton, B H; Barger, S W; Ohm, T G; Snow, A D 1993. Cellular and molecular pathology in Alzheimer's disease. Hippocampus, 3 Spec No , 271-87

Crutcher, K A; Scott, S A; Liang, S; Everson, W V; Weingartner, J 1993. Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience, 13 6, 2540-50

Crutcher, Keith A 1993. Fetal tissue research: the cutting edge? The Linacre quarterly, 60 2, 10-9

Liang, S; Crutcher, K A 1993. Movement of embryonic chick sympathetic neurons on laminin in vitro is preceded by neurite extension. Journal of neuroscience research, 36 6, 607-20

Crutcher, K A; Everson, W 1992. Fetal tissue. Nature, 357 6378, 432

Isaacson, L G; Saffran, B N; Crutcher, K A 1992. Nerve growth factor-induced sprouting of mature, uninjured sympathetic axons. The Journal of comparative neurology, 326 3, 327-36

Liang, S; Crutcher, K A 1992. Neuronal migration on laminin in vitro. Brain research. Developmental brain research, 66 1, 127-32

Crutcher, K A 1991. How to succeed in science. Perspectives in biology and medicine, 34 2, 213-8

Crutcher, K A; Neaderhauser, J; Schmidt, P; Weingartner, J 1991. Neurite outgrowth on postmortem human brain cryostat sections: studies of non-Alzheimer's and Alzheimer's tissue. Experimental neurology, 114 2, 228-36

Weil, S M; Madison, R D; Crutcher, K A 1991. Collagen nerve guide tubes in the rat septohippocampal pathway. Restorative neurology and neuroscience, 3 4, 167-75

Crutcher, K A 1990. Research on human embryos. Nature, 343 6253, 10

Crutcher, K A 1990. The regulation of axonal growth in the mature mammalian nervous system. Acta neurobiologiae experimentalis, 50 4-5, 115-24

Kesner, R P; Crutcher, K A; Omana, H 1990. Memory deficits following nucleus basalis magnocellularis lesions may be mediated through limbic, but not neocortical, targets. Neuroscience, 38 1, 93-102

Saffran, B N; Crutcher, K A 1990. NGF-induced remodeling of mature uninjured axon collaterals. Brain research, 525 1, 11-20

Collins, F; Crutcher, K A 1989. Sustained elevation in hippocampal NGF-like biological activity following medial septal lesions in the rat. Brain research, 490 2, 355-60

Crutcher, K A 1989. Tissue sections from the mature rat brain and spinal cord as substrates for neurite outgrowth in vitro: extensive growth on gray matter but little growth on white matter. Experimental neurology, 104 1, 39-54

Crutcher, K A; Privitera, M 1989. Axonal regeneration on mature human brain tissue sections in culture. Annals of neurology, 26 4, 580-3

Kesner, R P; Adelstein, T B; Crutcher, K A 1989. Equivalent spatial location memory deficits in rats with medial septum or hippocampal formation lesions and patients with dementia of the Alzheimer's type. Brain and cognition, 9 2, 289-300

Saffran, B N; Woo, J E; Mobley, W C; Crutcher, K A 1989. Intraventricular NGF infusion in the mature rat brain enhances sympathetic innervation of cerebrovascular targets but fails to elicit sympathetic ingrowth. Brain research, 492 1-2, 245-54

Cook, T M; Crutcher, K A 1988. Lesion-induced CA1 mossy fibers in the rat represent a neoinnervation. Experimental brain research, 70 2, 433-6

Crutcher, K A 1988. Fetal research ban. Science (New York, N.Y.), 242 4883, 1227

Crutcher, K A; Danscher, G; Geneser, F A 1988. Hippocampus and dentate area of the European hedgehog. Comparative histochemical study. Brain, behavior and evolution, 32 5, 269-76

Crutcher, K A; Marfurt, C F 1988. Nonregenerative axonal growth within the mature mammalian brain: ultrastructural identification of sympathohippocampal sprouts. The Journal of neuroscience : the official journal of the Society for Neuroscience, 8 7, 2289-302

Crutcher, K A 1987. Sympathetic sprouting in the central nervous system: a model for studies of axonal growth in the mature mammalian brain. Brain research, 434 2, 203-33

Kesner, R P; Adelstein, T; Crutcher, K A 1987. Rats with nucleus basalis magnocellularis lesions mimic mnemonic symptomatology observed in patients with dementia of the Alzheimer's type. Behavioral neuroscience, 101 4, 451-6

Kesner, R P; DiMattia, B V; Crutcher, K A 1987. Evidence for neocortical involvement in reference memory. Behavioral and neural biology, 47 1, 40-53

Saffran, B N; Crutcher, K A 1987. Putative gliotoxin, alpha-aminoadipic acid, fails to kill hippocampal astrocytes in vivo. Neuroscience letters, 81 1-2, 215-20

Cook, T M; Crutcher, K A 1986. Intrahippocampal injection of kainic acid produces significant pyramidal cell loss in neonatal rats. Neuroscience, 18 1, 79-92

Crutcher, K A 1986. The role of growth factors in neuronal development and plasticity. CRC critical reviews in clinical neurobiology, 2 3, 297-333

Crutcher, K A; Collins, F 1986. Entorhinal lesions result in increased nerve growth factor-like growth-promoting activity in medium conditioned by hippocampal slices. Brain research, 399 2, 383-9

Collins, F; Crutcher, K A 1985. Neurotrophic activity in the adult rat hippocampal formation: regional distribution and increase after septal lesion. The Journal of neuroscience : the official journal of the Society for Neuroscience, 5 10, 2809-14

Cook, T M; Crutcher, K A 1985. Extensive target cell loss during development results in mossy fibers in the regio superior (CA1) of the rat hippocampal formation. Brain research, 353 1, 19-30

Crutcher, K A; Chandler, J P 1985. Evidence for sprouting specificity following medial septal lesions in the rat. The Journal of comparative neurology, 237 1, 116-26

Crutcher, K A; Chandler, J P 1984. Association of basal lamina with peripheral axons elongating within the rat central nervous system. Brain research, 308 1, 177-81

Gibby, W A; Crutcher, K A 1984. Absence of sympathetic sprouting in the rat olfactory bulb after cholinergic denervation. Experimental neurology, 84 2, 386-95

Chandler, J P; Crutcher, K A 1983. The septohippocampal projection in the rat: an electron microscopic horseradish peroxidase study. Neuroscience, 10 3, 685-96

Crutcher, K A; Kesner, R P; Novak, J M 1983. Medial septal lesions, radial arm maze performance, and sympathetic sprouting: a study of recovery of function. Brain research, 262 1, 91-8

Crutcher, K A 1982. Neonatal septal lesions result in sympathohippocampal innervation in the adult rat. Experimental neurology, 76 1, 1-11

Crutcher, K A 1982. Development of the rat septohippocampal projection: a retrograde fluorescent tracer study. Brain research, 255 1, 145-50

Crutcher, K A; Collins, F 1982. In vitro Evidence for two distinct hippocampal growth factors: basis of neuronal plasticity? Science (New York, N.Y.), 217 4554, 67-8

Crutcher, K A; Davis, J N 1982. Target regulation of sympathetic sprouting in the rat hippocampal formation. Experimental neurology, 75 2, 347-59

Valdes, F; Dasheiff, R M; Birmingham, F; Crutcher, K A; McNamara, J O 1982. Benzodiazepine receptor increases after repeated seizures: evidence for localization to dentate granule cells. Proceedings of the National Academy of Sciences of the United States of America, 79 1, 193-7

Crutcher, K A 1981. Cholinergic denervation of rat neocortex results in sympathetic innervation. Experimental neurology, 74 1, 324-9

Crutcher, K A; Brothers, L; Davis, J N 1981. Sympathetic noradrenergic sprouting in response to central cholinergic denervation; a histochemical study of neuronal sprouting in the rat hippocampal formation. Brain research, 210 1-2, 115-28

Crutcher, K A; Davis, J N 1981. Sympathohippocampal sprouting is directed by a target tropic factor. Brain research, 204 2, 410-4

Crutcher, K A; Madison, R; Davis, J N 1981. A study of the rat septohippocampal pathway using anterograde transport of horseradish peroxidase. Neuroscience, 6 10, 1961-73

Madison, R; Crutcher, K A; Davis, J N 1981. Sympathohippocampal neurons are inside the blood--brain barrier. Brain research, 213 1, 183-9

Crutcher, K A; Davis, J N 1980. Noradrenergic sprouting in response to cholinergic denervation: the sympathohabenular connection. Experimental neurology, 70 1, 187-91

Crutcher, K A; Davis, J N 1980. Hippocampal alpha- and beta-adrenergic receptors: comparison of [3H]dihydroalprenolol and [3H]WB 4101 binding with noradrenergic innervation in the rat. Brain research, 182 1, 107-17

Giron, L T; Crutcher, K A; Davis, J N 1980. Lymph nodes--a possible site for sympathetic neuronal regulation of immune responses. Annals of neurology, 8 5, 520-5

Crutcher, K A; Brothers, L; Davis, J N 1979. Sprouting of sympathetic nerves in the absence of afferent input. Experimental neurology, 66 3, 778-83

Felten, D L; Crutcher, K A 1979. Neuronal-vascular relationships in the raphe nuclei, locus coeruleus, and substantia nigra in primates. The American journal of anatomy, 155 4, 467-81

Wagner, H R; Crutcher, K A; Davis, J N 1979. Chronic estrogen treatment decreases beta-adrenergic responses in rat cerebral cortex. Brain research, 171 1, 147-51

Crutcher, K A; Bingham, W G 1978. Descending monoaminergic pathways in the primate spinal cord. The American journal of anatomy, 153 1, 159-64

Crutcher, K A; Humbertson, A O 1978. The organization of monoamine neurons within the brainstem of the North American opossum (Didelphis virginiana). The Journal of comparative neurology, 179 1, 195-221

Crutcher, K A; Humbertson, A O; Martin, G F 1978. The origin of brainstem-spinal pathways in the North American opossum (Didelphis virginiana). Studies using the horseradish peroxidase method. The Journal of comparative neurology, 179 1, 169-93

Bierl, Michael A; Jones, Elizabeth E; Crutcher, Keith A; Isaacson, Lori G . 'Mature' nerve growth factor is a minor species in most peripheral tissues. Neuroscience letters, 380 1-2, 133-7

Carpenter, M K; Crutcher, K A; Kater, S B . An analysis of the effects of Alzheimer's plaques on living neurons. Neurobiology of aging, 14 3, 207-15

Crutcher, K A . Age-related decrease in sympathetic sprouting is primarily due to decreased target receptivity: implications for understanding brain aging. Neurobiology of aging, 11 3, 175-83

Crutcher, K A . Histochemical studies of sympathetic sprouting: fluorescence morphology of noradrenergic axons. Brain research bulletin, 9 1-6, 501-8

Crutcher, K A; Weingartner, J . Hippocampal NGF levels are not reduced in the aged Fischer 344 rat. Neurobiology of aging, 12 5, 449-54

Isaacson, L G; Crutcher, K A . Uninjured aged sympathetic neurons sprout in response to exogenous NGF in vivo. Neurobiology of aging, 19 4, 333-9

Isaacson, L G; Saffran, B N; Crutcher, K A . Intracerebral NGF infusion induces hyperinnervation of cerebral blood vessels. Neurobiology of aging, 11 1, 51-5

Kesner, R P; Crutcher, K A; Measom, M O . Medial septal and nucleus basalis magnocellularis lesions produce order memory deficits in rats which mimic symptomatology of Alzheimer's disease. Neurobiology of aging, 7 4, 287-95

Kuchel, G A; Crutcher, K A; Naheed, U; Thrasivoulou, C; Cowen, T . NGF expression in the aged rat pineal gland does not correlate with loss of sympathetic axonal branches and varicosities. Neurobiology of aging, 20 6, 685-93

Pettigrew, D B; Levin, L; Crutcher, K A . Sympathetic neurite growth on central nervous system sections is region-specific and unaltered by aging. Neurobiology of aging, 21 5, 629-38

Scott, S A; Crutcher, K A . Nerve growth factor and Alzheimer's disease. Reviews in the neurosciences, 5 3, 179-211

Scott, S A; Liang, S; Weingartner, J A; Crutcher, K A . Increased NGF-like activity in young but not aged rat hippocampus after septal lesions. Neurobiology of aging, 15 3, 337-46