Journal of neuroscience methods
-
J. Neurosci. Methods · Jun 2010
Neuroanatomical correlation of behavioral deficits in the CCI model of TBI.
Traumatic brain injury (TBI) is the leading cause of death and disability both in combat and civilian situations with limited treatment options including surgical removal of hematoma, ventricular drainage and use of hyperosmotic agents that restrict secondary injury following TBI. Availability of appropriate model system with full-range characterization of anatomical and behavioral components correlative with brain injury provides a pre-clinical platform to test candidate therapies for clinical translation. ⋯ Current investigation validated a detailed sensomotor and cognitive behavioral characterization correlative with diffuse axonal injury-the signature histopathology of TBI, in the CCI mouse model of TBI. Present study offers a comprehensively characterized model of TBI that can be used to investigate cellular and molecular mechanisms underlying TBI and to test candidate therapies in developing novel and effective treatments for TBI.
-
J. Neurosci. Methods · May 2010
Comparative StudyA comparison of two cognitive test paradigms in a penetrating brain injury model.
A rat model of penetrating ballistic-like brain injury (PBBI) was recently established to study military-relevant severe traumatic brain injury (TBI). The purpose of this study was to conduct a side-by-side evaluation of two well-established cognitive testing paradigms: the novel object recognition (NOR) task and the Morris water maze (MWM) task. ⋯ In contrast, PBBI produced consistent, significant spatial learning deficits in the MWM task. Overall, these results suggest that the MWM task provides a more appropriate cognitive test for the PBBI model that would be useful for testing promising neuroprotective therapeutics.
-
J. Neurosci. Methods · Apr 2010
The forced walking test: a novel test for pinpointing the anesthetic-induced transition in consciousness in mouse.
In consciousness or anesthesia studies, pinpointing the precise moment of consciousness or anesthetic transition has been challenging because of the variable lag time between a treatment and its induced response. Here, we describe a novel behavioral method, a forced walking test, which pinpoints the moment of the anesthetic-induced loss of motion (LOM) without handling the animals manually. The mouse is forced to walk on a treadmill, and an anesthetic drug is administered into the peritoneum via a previously secured injection route. ⋯ Comparison of our method with the conventional loss-of-righting-reflex assay showed that the time point of LOM was not significantly different between the two methods when examined with two different types of anesthetic agents, propofol and ketamine/xylazine cocktail. In addition, the electrophysiological signals simultaneously acquired in the cortex and the thalamus of the mouse during the forced walking test showed that the brain rhythms induced by ketamine/xylazine anesthesia were generated and terminated in a time-locked manner with respect to LOM and ROM, respectively. In conclusion, the forced walking test allows an objective and precise detection of anesthetic-induced LOM, as well as ROM during awakening from anesthesia, in test animals.
-
J. Neurosci. Methods · Apr 2010
A new thermal stimulation method for human psychophysical studies: pain intensity clamping.
A method for testing changes in pain sensitivity of human subjects over the course of prolonged thermal stimulation is introduced. It uses a Peltier-device-based thermode to generate a thermal contact stimulus, an electronic visual analog scale to continuously record the pain intensity and a system that controls selected stimulus parameters (temperature or pulse timing) as a function of the pain intensity rating. ⋯ Advantages of the method are that it automatically finds the stimulus magnitude that elicits predetermined pain intensity, regardless of how sensitive or insensitive the subject is, and it allows prolonged stimulation, because it does not allow pain intensity to escalate to unacceptable levels due to progressive sensitization. The subject is blinded regarding experimental effects because average pain intensity remains constant regardless of sensitization or pharmacological interventions.
-
J. Neurosci. Methods · Apr 2010
Evaluating the impact of the deep brain stimulation induced electric field on subthalamic neurons: a computational modelling study.
Deep brain stimulation (DBS) is an effective surgical treatment used to alleviate the symptoms of neurological disorders, most commonly movement disorders. However, the mechanism of how the applied stimulus pulses interact with the surrounding neuronal elements is not yet clearly understood, slowing progress and development of this promising therapeutic technology. To extend previous approaches of using isolated, myelinated axon models used to estimate the effect of DBS, we propose that taking into account entire neurons will reveal stimulation induced effects overlooked by previous studies. ⋯ Our results demonstrate that STN neurons have a higher excitation threshold than axons, as stimulus amplitudes 10 times as large elicit a VTA range a fifth of the distance from the electrode surface. However, the STN neurons do show a change in background firing rate in response to stimulation, even when they are classified as sub-threshold by the VTA definition. Furthermore the whole neuron models are sensitive to regions of high current density, as the distribution of firing is centred on the electrode contact edges These results demonstrate the importance of accurate neuron models for fully appreciating the spatial effects of DBS on the immediate surrounding brain volume within small distances of the electrode, which are overlooked by previous models of isolated axons and individual neurons.