Positive Allosteric Modulation of Cholinergic Receptors Improves Spatial Learning after Cortical Contusion Injury in Mice.

We examined benzyl quinolone carboxylic acid (BQCA), a novel M1 muscarinic-positive allosteric modulator, for improving memory and motor dysfunction after cerebral cortical contusion injury (CCI). Adult mice received unilateral motorsensory cortical CCI or sham injury. Benzyl quinolone carboxylic acid (BQCA; 5, 10, and 20 mg/kg, intraperitoneally [i.

Thyroid hormone treatment activates protective pathways in both in vivo and in vitro models of neuronal injury.

Thyroid hormone plays an important role in brain development and adult brain function, and may influence neuronal recovery after Traumatic Brain Injury (TBI). We utilized both animal and cell culture models to determine the effects of thyroid hormone treatment, post TBI or during hypoxia, on genes important for neuronal survival and neurogenesis. We show that TBI in rats is associated with a reduction in serum thyroxine (T4) and triiodothyronine (T3).

Dry-contact microelectrode membranes for wireless detection of electrical phenotypes in neonatal mouse hearts.

Continuous monitoring of aberrant electrical rhythms during heart injury and repair requires prolonged data acquisition. We hereby developed a wearable microelectrode membrane that could be adherent to the chest of neonatal mice for in situ wireless recording of electrocardiogram (ECG) signals. The novel dry-contact membrane with a meshed parylene-C pad adjacent to the microelectrodes and the expandable meandrous strips allowed for varying size of the neonates.

Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain.

Current rodent connectome projects are revealing brain structural connectivity with unprecedented resolution and completeness. How subregional structural connectivity relates to subregional functional interactions is an emerging research topic. We describe a method for standardized, mesoscopic-level data sampling from autoradiographic coronal sections of the rat brain, and for correlation-based analysis and intuitive display of cortico-cortical functional connectivity (FC) on a flattened cortical map.

Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos.

Chlorpyrifos (CPF) is an organophosphorus cholinesterase inhibitor widely used as an insecticide. Neuro and genotoxicity of this agent were evaluated following daily subcutaneous injections at 0.1, 1 and 10mg/kg or its vehicle to laboratory rats during one week, at the end of which somatosensory evoked potentials (SEP) and power spectrum of the electroencephalogram (EEGp) were recorded under urethane anesthesia.

Arginine NO-dependent and NO-independent effects on hemodynamics.

L-arginine administration decreases mean arterial blood pressure (MABP), presumably by excess nitric oxide (NO) synthesis. However, some reports indicate that d-arginine, not a substrate of NO synthase (NOS), also induces hypotension. To clarify this phenomenon, the hemodynamic effects of L- and D-arginine and their modification by NOS inhibition with L-nitroarginine methyl ester (L-NAME) were assessed.

Repeated blast exposure alters open field behavior recorded under low illumination.

Blast-induced traumatic brain injury (bTBI) can have devastating behavioral consequences. This study was designed to evaluate the behavioral consequences of single or repeated bTBI, as evaluated by an open field (OF) test conducted in near-darkness to avoid confounding effects of illumination and photophobia. Sprague-Dawley rats under isoflurane anesthesia were exposed to a series of 3 sub-lethal blasts into a compressed air-driven blast chamber separated by 2 week intervals (n=11).

Remote brain network changes after unilateral cortical impact injury and their modulation by acetylcholinesterase inhibition.

We explored whether cerebral cortical impact injury (CCI) effects extend beyond direct lesion sites to affect remote brain networks, and whether acetylcholinesterase (AChE) inhibition elicits discrete changes in functional activation of motor circuits following CCI. Adult male rats underwent unilateral motor-sensory CCI or sham injury. Physostigmine (AChE inhibitor) or saline were administered subcutaneously continuously via implanted minipumps (1.

Acetylcholinesterase inhibition interacts with training to reverse spatial learning deficits after cortical impact injury.

Cholinergic mechanisms are known to play a key role in cognitive functions that are profoundly altered in traumatic brain injury (TBI). The present investigation was designed to test the ability of continuous administration, starting at the time of injury, of physostigmine (PHY), an acetylcholinesterase (AChE) inhibitor that crosses the blood-brain barrier (BBB), to ameliorate the alterations of learning and memory induced by cerebral cortex impact injury in rats under isoflurane anesthesia. Learning and memory were assessed with the Morris water maze implemented during days 7-11 (WM1), and days 21-25 post-TBI (WM2), with four trials per day for 3 days, followed by target reversal and 2 additional days of training.

Calf tissue oxygenation during exercise in men with and without risk factors for developing peripheral arterial disease.

Objective: This study aimed to compare calf tissue oxygenation responses to calf exercise in men without diagnosed peripheral arterial disease but with selected risk factors for peripheral arterial disease with those without risk factors.

Design: A cross-sectional quasi-experimental design was used. The no-risk group (n = 20) had none of the risk factors (diabetes, hypertension, hyperlipidemia, obesity, current or 10 pack-yr smoking history, or age ≥65 yrs).

Acetylcholinesterase inhibition and locomotor function after motor-sensory cortex impact injury.

Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex.

The environmental pollutant endosulfan disrupts cerebral cortical function at low doses.

Endosulfan can induce convulsions that could lead to brain damage. The variability and lack of specificity of neurological signs and symptoms in the pre-convulsive stages makes early diagnosis difficult. We sought to determine if electrophysiological exploration of the cerebral cortex could yield objective signs of endosulfan intoxication at levels that do not elicit convulsions.

Ergometric performance during exercise training in men with intermittent claudication.

Objective: To determine and describe changes in weekly work, power, exercise times, and recovery times during an exercise training intervention in men with peripheral arterial disease (PAD) and intermittent calf claudication.

Design: Tracking of weekly exercise training parameters involved repeated measures over time in one group of participants. Other outcomes of this pilot study used a one-group, pretest-posttest design.

Preamputation evaluation of lower-limb skeletal muscle perfusion with H(2) (15)O positron emission tomography.

Objective: To establish whether muscle blood flow (MBF) measurements with O-water positron emission tomography could reliably identify patients with critical limb ischemia and detect and quantify a distal deficit in skeletal MBF in these cases.

Design: O-water positron emission tomography scans were performed at rest or during unloaded ankle plantar and dorsiflexion exercise of the diseased leg in 17 subjects with leg ischemia or on a randomly selected leg of 18 age-matched healthy control subjects. TcPO2 was evaluated with Novametrix monitors and perfusion of skin topically heated to 44 degrees C and adjacent nonheated areas with a Moor Instruments laser Doppler imaging scanner.

Preamputation evaluation of limb perfusion with laser Doppler imaging and transcutaneous gases.

We studied 31 subjects with severe leg ischemia and 29 age-matched nonischemic control subjects to compare preamputation assessments of leg ischemia using laser Doppler imaging (LDI), transcutaneous partial pressure of oxygen (TcPO(2)), and transcutaneous partial pressure of carbon dioxide (TcPCO(2)). TcPO(2) and TcPCO(2) were evaluated with Novametrix Medical Systems, Inc, monitors (Wallingford, Connecticut) and perfusion (flux) of skin topically heated to 44 degrees C, and adjacent nonheated areas were evaluated with a Moor Laser Doppler Imager (Moor Instruments, Ltd; Devon, England). LDI flux of heated areas, its ratio to nonheated areas, and TcPO(2) (not TcPCO(2)) were lower in ischemic subjects than in control subjects.

Scanning laser-Doppler imaging of leg- and foot-skin perfusion in normal subjects: analysis of age, gender, site, and laser-type effects.

Objectives: To report normal values of skin perfusion in healthy subjects in three age groups using a laser Doppler imager; to determine differences attributable to gender, age, site, and use of red or near-infrared lasers; and to correlate transcutaneous oxygen with laser flux values.

Design: Flux and transcutaneous oxygen were measured at ten sites in the lower extremity in 60 subjects from three age groups. Heated and unheated sites were scanned with red and near-infrared lasers.

Pilot studies to demonstrate that intestinal mucosal afferent nerves are functionally linked to visceral adipose tissue.

Dietary capsaicin reduces rodent visceral fat weight. We tested the hypothesis that intact intestinal mucosal afferent nerve function is necessary for fat deposition in visceral adipose tissue sites. Rats were treated daily for 2 weeks with intragastric (chronic treatment) vehicle or capsaicin.

Acetylcholine and choline dynamics provide early and late markers of traumatic brain injury.

We assessed acetylcholine (ACh) and choline (Ch) dynamics 2.5 h, 1, 4 and 14 days after cerebral cortex impact injury or craniotomy only in adult male Sprague-Dawley rats. Cortical endogenous ACh (D0ACh), endogenous free Ch (D0Ch), deuterium-labeled Ch (D4Ch), and ACh synthesized from D4Ch (D4ACh) were measured by gas-chromatography mass-spectrometry after intravenous injection of D4Ch followed in 1 min by microwave fixation of the brain.

Circadian rhythms of heart rate and locomotion after treatment with low-dose acetylcholinesterase inhibitors.

This study tested the hypothesis that repeated exposure to low levels of sarin, pyridostigmine bromide (PB) or their combination, at doses equivalent to those possibly experienced by veterans of the 1991 Persian Gulf War, could lead to persistent or delayed autonomic effects and thus help to explain the cause of clinical findings in this population. Male Sprague-Dawley rats were treated for 3 weeks with: saline injection (0.5 ml kg(-1), s.

Cerebral acetylcholine and choline contents and turnover following low-dose acetylcholinesterase inhibitors treatment in rats.

Male Sprague-Dawley rats were treated for 3 weeks with (1) regular tap drinking water plus subcutaneous (s.c.) saline (0.

Low-dose cholinesterase inhibitors do not induce delayed effects on cerebral blood flow and metabolism.

The acetylcholinesterase (AChE) inhibitors sarin and pyridostigmine bromide (PB) have been proposed as causes of neurobehavioral dysfunction in Persian Gulf War veterans. To test possible delayed effects of these agents, we exposed rats to low (subsymptomatic) levels of sarin (0.5 LD50 s.

Measurement of cardiac output with indocyanine green transcutaneous fluorescence dilution technique.

Background: Cardiac output is an essential parameter for the hemodynamic assessment of patients with cardiovascular disease. The authors tested in an animal model the feasibility of measuring cardiac output by transcutaneous fluorescence monitoring of an intravenous bolus injection of indocyanine green.

Methods: Fluorescence dilution cardiac output was measured in 10 anesthetized rabbits and compared with cardiac output measured with a pulmonary thermodilution catheter and to aortic velocity measured by Doppler ultrasound.

Delayed neurologic and behavioral effects of subtoxic doses of cholinesterase inhibitors.

We tested the hypothesis that pyridostigmine bromide (PB) intake and/or low-level sarin exposure, suggested by some as causes of the symptoms experienced by Persian Gulf War veterans, induce neurobehavioral dysfunction that outlasts their effects on cholinesterase. Adult male Sprague-Dawley rats were treated during 3 weeks with s.c.