Faculty Book
IAN D. HENTALL, PH.D.
Research Associate Professor, Department of Neurological Surgery
Brainstem stimulation for spinal injury; serotonin in spinal motor and sensory control; dietary restriction; brain stimulation techniques
Research
Interests
My main research is on electrical stimulation of the brain to promote general motor and sensory recovery from spinal cord injury. We discovered in 2007 that a few days of stimulation, applied to a cell group in the brainstem whose axons release serotonin in the spinal cord, can greatly improve functional recovery early after incomplete thoracic contusion injury in rats. We are now testing this effect on chronic injuries and in combination with an anti-inflammatory agent. We are also examining an alternative stimulation site in the midbrain, in a region occasionally targeted for chronic deep brain stimulation in people with severe non-malignant pain. Much of this effort is devoted to the design and fabrication of very small, low-power and long-lasting stimulator implants. These implants are controlled remotely by 2-way magnetic and infrared communication and deliver complex daily patterns of electrical pulse trains. This bioelectronics emphasis originates in my long-standing research program on the theory and methodology of electrical brain stimulation. In recent years, for example, I developed a novel technique for minimally invasive brain mapping that uses coincident stimulation and recording through a single electrode. Although its advantages were first demonstrated in rat models of epilepsy, the method offers novel possibilities for various tasks in experimental and clinical neuroscience. We are also currently pursuing the basic mechanisms underlying brainstem-elicited spinal cord repair, in a continuing collaboration with Dr Brian Noga’s laboratory in The Miami Project, by mapping the levels serotonin in the spinal cord. We have explored not only release following descending brainstem activity, but also during acute thoracic injury and fictive locomotion. Our high-resolution mapping technique, which detects serotonin and other substances electrochemically with a microelectrode, has also benefited from in-house innovations in instrumentation, including a method for simultaneous detection from multiple sites. Therapeutic delivery of monoamines, such as serotonin and norepinephrine, can alternatively be achieved by release from transplanted cells. A collaboration with Dr. Jacqueline Sagen of The Miami Project concerns spinally implanted chromaffin cells. We are analyzing at the single-cell level the circuitry that is responsible for the well established analgesic effect of these monoamine-releasing cells. My final research area concerns the effects of dietary restriction on spinal cord pathologies, a joint study with Dr. Walter Hargraves of the University of Illinois, Chicago. We have shown that a sustained low calorie diet greatly reduces chronic pain and arthritis in mice, but have so far found mostly detrimental effects of dietary restriction on spinal cord repair. We did find, however, that calorie intake has a significant impact on early recovery from spinal injury, and are following up these nutritional studies as well as expanding the work on electrical brainstem stimulation. Our strategic emphasis therefore stays on basic research that can quickly lead to practical ways of boosting the incomplete recovery that is typically seen after spinal cord injury.
Recent References
Hentall ID, Noga BR, Sagen J. 2001. Spinal transplants of adrenal medulla block nociceptive facilitation in the dorsal horn. J. Neurophysol. 85, 1788-1792.
Hentall ID, Pinzon A, Mesigil RP, Noga BR. 2003. Temporal and spatial profiles of pontine-evoked monoamine release in the rat's spinal cord. J. Neurophysol. 89, 2943-2951.
Noga BR, Pinzon A, Mesigil RP, Hentall ID. 2004 Steady state levels of monoamines in the rat lumbar spinal cord – spatial mapping and the effect of acute spinal cord injury. J. Neurophysol. 92, 567-577.
Hentall ID. 2004. Detection of abnormal cerebral excitability by coincident stimulation and recording. Clin. Neurophysiol. 115, 2502-2510.
Hargraves WA, Hentall ID. 2005. Analgesic effects of chronic caloric restriction in the adult mouse. Pain 114, 455-61.
Hentall ID, Pinzon A, Noga BR. 2006. Spatial and temporal patterns of serotonin release in the rat's lumbar spinal cord following electrical stimulation of the nucleus raphe magnus. Neuroscience. 142, 893-903.
Brumley MR, Hentall ID, Pinzon A, Kadam BH, Blythe A, Sanchez FJ, Taberner AM, Noga BR. 2007. Serotonin concentrations in the lumbosacral spinal cord of the adult rat following microinjection or dorsal surface application. J Neurophysiol. 98, 1440-1450.
Hentall ID, Hargraves WA, Sagen J. 2007. Inhibition by the chromaffin cell-derived peptide serine-histogranin in the rat's dorsal horn. Neurosci Lett. 419, 88-92.
Last update: October, 2007
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