Complete protection from impending stroke following permanent middle cerebral artery occlusion in awake, behaving rats.

Using a rodent model of ischemic stroke [permanent middle cerebral artery occlusion (pMCAO)], our laboratory has previously demonstrated that sensory-evoked cortical activation via mechanical single whisker stimulation treatment delivered under an anesthetized condition within 2 h of ischemic onset confers complete protection from impending infarct. There is a limited time window for this protection; rats that received the identical treatment at 3 h following ischemic onset lost neuronal function and sustained a substantial infarct. Rats in these studies, however, were anesthetized with sodium pentobarbital or isoflurane, whereas most human stroke patients are typically awake.

Sensory Stimulation-Based Complete Protection from Ischemic Stroke Remains Stable at 4 Months Post-Occlusion of MCA.

Previous research from our lab has shown that when using a rodent model of ischemic stroke (permanent middle cerebral artery occlusion), mild sensory stimulation, when delivered within two hours of ischemic onset, completely protects the cortex from impending ischemic stroke damage when assessed 24 hours post-occlusion. However, the long-term stability of this protection remains unclear. Using intrinsic signal optical imaging for assessment of cortical function, laser speckle imaging for assessment of blood flow, a battery of behavioral tests and cresyl violet for histological assessment, the present study examined whether this protection was long-lasting.

Permanent cerebral vessel occlusion via double ligature and transection.

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow (ischemia). Middle cerebral artery (MCA) delivers a great majority of blood to the lateral surface of the cortex, is the most common site of human stroke, and ischemia within its territory can result in extensive dysfunction or death.

Early stimulation treatment provides complete sensory-induced protection from ischemic stroke under isoflurane anesthesia.

Using a rodent model of ischemia [permanent middle cerebral artery occlusion (pMCAO)], previous studies demonstrated that whisker stimulation treatment completely protects the cortex from impending stroke when initiated within 2 h following pMCAO. When initiated 3 h post-pMCAO, the identical treatment exacerbates stroke damage. Rats in these studies, however, were anesthetised with sodium pentobarbital, whereas human stroke patients are typically awake.

Mild sensory stimulation protects the aged rodent from cortical ischemic stroke after permanent middle cerebral artery occlusion.

Background: Accumulated research has shown that the older adult brain is significantly more vulnerable to stroke than the young adult brain. Although recent evidence in young adult rats demonstrates that single-whisker stimulation can result in complete protection from ischemic damage after permanent middle cerebral artery occlusion (pMCAO), it remains unclear whether the same treatment would be effective in older animals.

Methods And Results: Aged rats (21 to 24 months of age) underwent pMCAO and subsequently were divided into "treated" and "untreated" groups.

A rat's whiskers point the way toward a novel stimulus-dependent, protective stroke therapy.

Stroke is the fourth leading cause of death in the United States and the leading cause of long-term disability. Ischemic stroke, due to an interruption in blood supply, is particularly prevalent; 87% of all strokes are ischemic. Unfortunately, current options for acute treatment are extremely limited and there is a great need for new treatment strategies.

Mild sensory stimulation reestablishes cortical function during the acute phase of ischemia.

When delivered within 1 and in most cases 2 h of permanent middle cerebral artery occlusion (pMCAO), mild sensory stimulation (intermittent single whisker stimulation) was shown to be completely neuroprotective 24 h after pMCAO in a rodent model of ischemic stroke, according to assessment with multiple techniques (Lay et al., 2010). The acute effect of stimulation treatment on the ischemic cortex, however, has yet to be reported.

Amount but not pattern of protective sensory stimulation alters recovery after permanent middle cerebral artery occlusion.

Background And Purpose: Using a rodent model of ischemia (permanent middle cerebral artery occlusion), our laboratory previously demonstrated that 4.27 minutes of patterned single-whisker stimulation delivered over 120 minutes can fully protect from impending damage when initiated within 2 hours of permanent middle cerebral artery occlusion ("early"). When initiated 3 hours postpermanent middle cerebral artery occlusion ("late"), stimulation resulted in irreversible damage.

Mild sensory stimulation completely protects the adult rodent cortex from ischemic stroke.

Despite progress in reducing ischemic stroke damage, complete protection remains elusive. Here we demonstrate that, after permanent occlusion of a major cortical artery (middle cerebral artery; MCA), single whisker stimulation can induce complete protection of the adult rat cortex, but only if administered within a critical time window. Animals that receive early treatment are histologically and behaviorally equivalent to healthy controls and have normal neuronal function.

Intrinsic signal optical imaging of brain function using short stimulus delivery intervals.

Intrinsic signal optical imaging (ISOI) can be used to map cortical function and organization. Because its detected signal lasts 10+s consisting of three phases, trials are typically collected using a long (tens of seconds) stimulus delivery interval (SDI) at the expense of efficiency, even when interested in mapping only the first signal phase (e.g.

Imaging cortical absorption, scattering, and hemodynamic response during ischemic stroke using spatially modulated near-infrared illumination.

We describe a technique that uses spatially modulated near-infrared (NIR) illumination to detect and map changes in both optical properties (absorption and reduced scattering parameters) and tissue composition (oxy- and deoxyhemoglobin, total hemoglobin, and oxygen saturation) during acute ischemic injury in the rat barrel cortex. Cerebral ischemia is induced using an open vascular occlusion technique of the middle cerebral artery (MCA). Diffuse reflected NIR light (680 to 980 nm) from the left parietal somatosensory cortex is detected by a CCD camera before and after MCA occlusion.

Robust and stable drinking behavior following long-term oral alcohol intake in rhesus macaques.

Face validity in animal models of alcohol abuse and dependence is often at odds with robust demonstrations of ethanol-seeking. This study determined the relative influence of ethanol and a flavorant in maintaining ethanol intake in a nonhuman primate model of "cocktail" drinking. Four-year-old male monkeys were maintained on a 6% ethanol/6% Tang solution made available in daily (M-F) 1-h sessions.

Impact of ambient temperature on hyperthermia induced by (+/-)3,4-methylenedioxymethamphetamine in rhesus macaques.

The ambient temperature (T(A)) under which rodents are exposed to (+/-)3,4-methylenedioxymethamphetamine (MDMA) affects the direction and magnitude of the body temperature response, and the degree of hypo/hyperthermia generated in subjects can modify the severity of lasting brain changes in 'neurotoxicity' models. The thermoregulatory effects of MDMA have not been well described in non-human primates and it is unknown if T(A) has the potential to affect acute hyperthermia and therefore other lasting consequences of MDMA. The objective of this study was to determine if the temperature alteration produced by MDMA in nonhuman primates depends on T(A) as it does in rats and mice.

Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys.

Rationale: Dopaminergic neurotransmission is critically involved in many aspects of complex behavior and cognition beyond reward/reinforcement and motor function. Mental and behavioral disorders associated with major disruptions of dopamine neurotransmission, including schizophrenia, attention deficit/hyperactivity disorder, Parkinson's disease, Huntington's disease, and substance abuse produce constellations of neuropsychological deficits in learning, memory, and attention in addition to other defining symptoms.

Objective: To delineate the role dopaminergic D1- and D2-like receptor subtypes play in complex brain functions.

Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys.

Background: Exposure to (+/-)3,4-methylenedioxymethamphetamine ((+/-)MDMA) results in lasting reductions of many markers for serotonin terminals in a range of species. In rodents, the severity of insult depends in large part on the generation of hyperthermia in the subject. (+/-)MDMA can produce either hyperthermia or hypothermia in rodents depending on the ambient temperature and these effects may be limited to the S(+) enantiomer.

Development of a chipscale integrated microelectrode/microelectronic device for brain implantable neuroengineering applications.

An ultralow power analog CMOS chip and a silicon based microelectrode array have been fully integrated to a microminiaturized "neuroport" for brain implantable neuroengineering applications. The CMOS integrated circuit (IC) includes preamplifier and multiplexing circuitry, and a hybrid flip-chip bonding technique was developed to fabricate a functional, encapsulated microminiaturized neuroprobe device. Our neuroport has been evaluated using various methods, including pseudospike detection and local excitation measurement, and showed suitable characteristics for recording neural activities.

A microelectrode/microelectronic hybrid device for brain implantable neuroprosthesis applications.

We have designed, fabricated, and characterized a microminiaturized "neuroport" for brain implantable neuroprosthesis applications, using an analog CMOS integrated circuit and a silicon based microelectrode array. An ultra-low power, low-noise CMOS preamplifier array with integral multiplexing was designed to accommodate stringent thermal and electrophysiological requirements for implantation in the brain, and a hybrid integration approach was developed to fabricate a functional microminiaturized neuroprobe device. Measurements showed that our fully scalable 16-channel CMOS amplifier chip had an average gain of 44 dB, bandwidth from 10 Hz to 7.

Controlled and behaviorally relevant levels of oral ethanol intake in rhesus macaques using a flavorant-fade procedure.

Background: Flavorant-fading procedures can initiate and maintain oral ethanol intake in rodents. The present study developed a similar procedure to achieve controlled and behaviorally relevant levels of ethanol intake in monkeys.

Methods: Male rhesus macaques (N = 13) were initially given the opportunity to consume 0.