Vasodilator dysfunction and oligodendrocyte dysmaturation in aging white matter.

Objective: Microvascular brain injury (mVBI) is a common pathological correlate of vascular contributions to cognitive impairment and dementia (VCID) that leads to white matter (WM) injury (WMI). VCID appears to arise from chronic recurrent white matter ischemia that triggers oxidative stress and an increase in total oligodendrocyte lineage cells. We hypothesized that mVBI involves vasodilator dysfunction of white matter penetrating arterioles and aberrant oligodendrocyte progenitor cell (OPC) responses to WMI.

Unbiased Stereological Analysis of Reactive Astrogliosis to Estimate Age-Associated Cerebral White Matter Injury.

Cerebral white matter injury (WMI) contributes to cognitive dysfunction associated with pathological aging. Because reactive astrocyte-related factors contribute to remyelination failure after WMI, we sought accurate, cost-effective, and reproducible histopathological approaches for quantification of morphometric features of reactive astrogliosis in aged human white matter in patients with vascular brain injury (VBI). We compared 7 distinct approaches to quantify the features of glial fibrillary acidic protein (GFAP)-labeled astrocytes in the prefrontal white matter of brains from patients with VBI (n = 17, mean age 88.

Recovery of precision grasping after motor cortex lesion does not require forced use of the impaired hand in Macaca mulatta.

We investigated recovery of precision grasping of small objects between the index finger and thumb of the impaired hand without forced use after surgically placed lesions to the hand/arm areas of M1 and M1 + lateral premotor cortex in two monkeys. The unilateral lesions were contralateral to the monkey's preferred hand, which was established in prelesion testing as the hand used most often to acquire raisins in a foraging board (FB) task in which the monkey was free to use either hand to acquire treats. The lesions initially produced a clear paresis of the contralesional hand and use of only the ipsilesional hand to acquire raisins in the FB task.

Importance of proximal A2 and A4 pulleys to maintaining kinematics in the hand: a biomechanical study.

Purpose: The A2 and A4 pulleys have been shown to be important in finger flexor tendon function. Other authors have suggested either reconstruction or venting of portions of these pulleys in an attempt to preserve finger function in certain clinical situations. This study examines the effects of partial incision of these pulleys on finger flexion kinematics and biomechanics.

Terminal distribution of the corticospinal projection from the hand/arm region of the primary motor cortex to the cervical enlargement in rhesus monkey.

To further our understanding of the corticospinal projection (CSP) from the hand/arm representation of the primary motor cortex (M1), high-resolution anterograde tracing methodology and stereology were used to investigate the terminal distribution of this connection at spinal levels C5 to T1. The highest number of labeled terminal boutons occurred contralaterally (98%) with few ipsilaterally (2%). Contralaterally, labeled boutons were located within laminae I-X, with the densest distribution found in lamina VII and, to a lesser extent, laminae IX and VI.

Plasticity of cerebral functions.

Over the past two decades, results from neurophysiological studies in animal models and neuroimaging studies in human populations have converged along a common thread. Neuroplasticity in the remaining, intact tissue accompanies functional recovery after brain injury. Now, virtually every new therapeutic approach in postinjury rehabilitation relies on the fundamental principles of neuroplasticity for theoretical validity.

Volumetric effects of motor cortex injury on recovery of ipsilesional dexterous movements.

Damage to the motor cortex of one hemisphere has classically been associated with contralateral upper limb paresis, but recent patient studies have identified deficits in both upper limbs. In non-human primates, we tested the hypothesis that the severity of ipsilesional upper limb motor impairment in the early post-injury phase depends on the volume of gray and white matter damage of the motor areas of the frontal lobe. We also postulated that substantial recovery would accompany minimal task practice and that ipsilesional limb recovery would be correlated with recovery of the contralesional limb.

Minimal forced use without constraint stimulates spontaneous use of the impaired upper extremity following motor cortex injury.

The purpose of this study was to determine if recovery of neurologically impaired hand function following isolated motor cortex injury would occur without constraint of the non-impaired limb, and without daily forced use of the impaired limb. Nine monkeys (Macaca mulatta) received neurosurgical lesions of various extents to arm representations of motor cortex in the hemisphere contralateral to the preferred hand. After the lesion, no physical constraints were placed on the ipsilesional arm/hand and motor testing was carried out weekly with a maximum of 40 attempts in two fine motor tasks that required use of the contralesional hand for successful food acquisition.

Selective long-term reorganization of the corticospinal projection from the supplementary motor cortex following recovery from lateral motor cortex injury.

Brain injury affecting the frontal motor cortex or its descending axons often causes contralateral upper extremity paresis. Although recovery is variable, the underlying mechanisms supporting favorable motor recovery remain unclear. Because the medial wall of the cerebral hemisphere is often spared following brain injury and recent functional neuroimaging studies in patients indicate a potential role for this brain region in the recovery process, we investigated the long-term effects of isolated lateral frontal motor cortical injury on the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2).

Volumetric effects of motor cortex injury on recovery of dexterous movements.

Due to the heterogeneous nature of most brain injuries, the contributions of gray and white matter involvement to motor deficits and recovery potential remain obscure. We tested the hypothesis that duration of hand motor impairment and recovery of skilled arm and hand motor function depends on the volume of gray and white matter damage of the frontal lobe. Lesions of the primary motor cortex (M1), M1 + lateral premotor cortex (LPMC), M1 + LPMC + supplementary motor cortex (M2) or multifocal lesions affecting motor areas and medial prefrontal cortex were evaluated in rhesus monkeys.

Prolonged microgliosis in the rhesus monkey central nervous system after traumatic brain injury.

Impaired fine motor functions after traumatic brain injury (TBI) in humans and non-human primates often continue to improve months after injury. To initiate a series of studies in the primate model designed to investigate possible involvement of microglia/macrophage in the long-term recovery processes, changes in these cells were studied in the rhesus monkey central nervous system at 1, 6, and 12 months after a combined unilateral lesion of the arm area of the primary motor cortex and arm area of the lateral premotor cortex. Immunohistological studies showed profound CD68 immunoreactivity in the lesion area and the contralateral lateral corticospinal tract in the spinal cord at all time points, demonstrating that microglia/macrophage remain reactive at the sites of injury and axonal degeneration/survival for at least 12 months.

Localization of arm representation in the cerebral peduncle of the non-human primate.

Motor deficit severity and the potential for recovery in patients with brain injury depend on the integrity of descending corticofugal projections. Clinical assessment of these conditions following subtotal brain trauma requires a comprehensive understanding of the anatomical structures involved in the lesion as well as those structures that are spared. To assist in this endeavor, we investigated motor fiber organization in the crus cerebri of the cerebral peduncle (ccCP) in the rhesus monkey.

Measurement of reaching kinematics and prehensile dexterity in nonhuman primates.

A modified "Klüver" or dexterity board was developed to assess fine control of hand and digit movements by nonhuman primates during the acquisition of small food pellets from wells of different diameter. The primary advantages of the new device over those used previously include standardized positioning of target food pellets and controlled testing of each hand without the need for restraints, thereby allowing the monkey to move freely about the cage. Three-dimensional video analysis of hand motion was used to provide measures of reaching accuracy and grip aperture, as well as temporal measures of reach duration and food-pellet manipulation.

Amygdala interconnections with the cingulate motor cortex in the rhesus monkey.

Amygdala interconnections with the cingulate motor cortices were investigated in the rhesus monkey. Using multiple tracing approaches, we found a robust projection from the lateral basal nucleus of the amygdala to Layers II, IIIa, and V of the rostral cingulate motor cortex (M3). A smaller source of amygdala input arose from the accessory basal, cortical, and lateral nuclei, which targeted only the rostral region of M3.

Experimental investigation of finger dynamics before and after metacarpophalangeal joint arthroplasty.

Purpose: The purpose of this study was to quantify the changes in the arc of digital flexion before and after metacarpophalangeal (MCP) silicone arthroplasty with a 30 degrees preflexed design.

Methods: Index, middle, and ring fingers of 4 fresh-frozen cadaver hands were used. Each hand was attached (palmar side up) to a custom test apparatus.

Measurement of coordination of object manipulation in non-human primates.

We present a modification of the automated movement assessment panel [Gash DM, Zhang Z, Umberger G, Mahood K, Smith M, Smith C, et al. An automated movement assessment panel for upper limb motor functions in rhesus monkeys and humans. J Neurosci Methods 1999;89:111-7] that incorporates a three-dimensional load cell to record forces applied by monkeys while manipulating food targets.

Lactate dehydrogenase-elevating virus induces apoptosis in cultured macrophages and in spinal cords of C58 mice coincident with onset of murine amyotrophic lateral sclerosis.

Age-dependent poliomyelitis (ADPM) or murine amyotrophic lateral sclerosis (ALS) is a murine paralytic disease triggered in immunosuppressed genetically-susceptible mice by infection with the arterivirus lactate dehydrogenase-elevating virus (LDV). This disease provides an animal model for ALS, affecting anterior horn neurons and resulting in neuroparalysis 2-3 weeks after LDV infection. We have tested the hypothesis that spinal cord apoptosis is a feature of the LDV-induced murine ALS, since apoptosis is postulated to be a causal factor in human ALS.