Biomedical subjects

D Michele Basso

Publications and source records attributed to D Michele Basso.

10 recordsLinked to original sources

PubMed2006

Delayed Nogo receptor therapy improves recovery from spinal cord contusion.

OBJECTIVE: Myelin-associated inhibitors play a role in limiting axonal growth in the adult central nervous system. Blocking these inhibitors may promote neurological recovery from spinal cord contusion. METHODS: The soluble Nogo-66 receptor (NgR(310)ecto-Fc) protein, which can neutralize three myelin inhibitors, was infused into rats after spinal cord contusion for 28 days. Treatment was initiated intrathecally at the time of injury or 3 days after injury by the intracerebroventricular route at a dose of 0.29 mg/kg/day. Recovery of locomotion and of axonal growth was assessed. Some animals received combination therapy with NgR(310)ecto-Fc plus rolipram, a cyclic adenosine monophosphate phosphodiesterase inhibitor. RESULTS: Seven weeks after spinal injury, the Basso-Beattie Bresnahan locomotor scores were significantly improved in the 3-day delayed NgR(310)ecto-Fc treatment group (9.5 +/- 0.7; n = 16) versus the vehicle-treated group, (6.75 +/- 0.7; n = 15) (p < or = 0.01, analysis of variance). The percentage of NgR(310)ecto-Fc-treated animals able to support their weight was twice that in the control group. Delayed therapy was as efficacious as acute therapy. Addition of rolipram did not alter recovery. The beneficial behavioral effects of NgR(310)ecto-Fc correlated with sprouting of raphespinal axons in the caudal spinal cord and of corticospinal axons in the rostral spinal cord. INTERPRETATION: NgR(310)ecto-Fc treatment improves outcome in a rodent model that closely mimicked human spinal cord injury.

Animals↗

PubMed2006

Development of the Hand Active Sensation Test: reliability and validity.

OBJECTIVE: To develop and establish the reliability and validity of a new quantitative functional measure of haptic perception in the hand, the Hand Active Sensation Test (HASTe). DESIGN: Reliability was assessed by test-retest sessions. Validity was assessed via discriminant analysis, concurrent validity with 2-point discrimination and wrist position test, and receiver operating characteristic (ROC) curve construction. SETTING: Subject preference. PARTICIPANTS: Heterogeneous sample of 28 stroke survivors and 28 individually matched controls. INTERVENTION: Subjects used 1 hand to manipulate HASTe objects that vary by weight or texture to complete 18 match-to-sample trials. MAIN OUTCOME MEASURES: Two-point discrimination threshold, Wrist Position Sense Test (WPST) average error, and HASTe accuracy score. RESULTS: Test-retest reliability was strong (intraclass correlation coefficient model 3,1 = .77). The HASTe score significantly discriminated the groups (t = 8.3, P < .001) and correlated with 2-point discrimination (r = -.67, P < .001) and WPST (r = -.60, P < .001). ROC curve area was .94 for test 1 and .92 for the average of 2 tests. CONCLUSIONS: The HASTe is a reliable and valid functional measure of haptic perception, appears to detect impairment of haptic perception even in stroke survivors with no reported sensory deficits, and may provide valuable quantitative clinical data about complex sensory loss and hand function after stroke.

Adult↗

PubMed2006

Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains.

Genetically engineered mice are used extensively to examine molecular responses to spinal cord injury (SCI). Inherent strain differences may confound behavioral outcomes; therefore, behavioral characterization of several strains after SCI is warranted. The Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB) for rats has been widely used for SCI mice, but may not accurately reflect their unique recovery pattern. This study's purpose was to develop a valid locomotor rating scale for mice and to identify strain differences in locomotor recovery after SCI. We examined C57BL/6, C57BL/10, B10.PL, BALB/c, and C57BL/6x129S6 F1 strains for 42 days after mild, moderate, and severe contusive SCI or transection of the mid thoracic spinal cord. Contusions were created using the Ohio State University electromagnetic SCI device which is a displacement-driven model, and the Infinite Horizon device, which is a force-driven model. Attributes and rankings for the Basso Mouse Scale for Locomotion (BMS) were determined from frequency analyses of seven locomotor categories. Mouse recovery differed from rats for coordination, paw position and trunk instability. Disagreement occurred across six expert raters using BBB (p < 0.05) but not BMS to assess the same mice. BMS detected significant differences in locomotor outcomes between severe contusion and transection (p < 0.05) and SCI severity gradations resulting from displacement variations of only 0.1 mm (p < 0.05). BMS demonstrated significant face, predictive and concurrent validity. Novice BMS raters with training scored within 0.5 points of experts and demonstrated high reliability (0.92-0.99). The BMS is a sensitive, valid and reliable locomotor measure in SCI mice. BMS revealed significantly higher recovery in C57BL/10, B10.PL and F1 than the C57BL/6 and BALB/c strains after moderate SCI (p < 0.05). The differing behavioral response to SCI suggests inherent genetic factors significantly impact locomotor recovery and must be considered in studies with inbred or genetically engineered mouse strains.

Animals↗

PubMed2005

Stepwise motor and all-or-none sensory recovery is associated with nonlinear sparing after incremental spinal cord injury in rats.

Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance. While more functional recovery occurs with greater white matter sparing (WMS), it is unclear which locomotor features are more vulnerable to SCI than others, if recovery of certain features depends on specific amounts of WMS, and whether motor recovery patterns differ from sensory recovery. Locomotor and sensory recovery after graded contusive SCI with cord displacements of 0.3, 0.5, 0.7, 0.9, 1.1, 1.25, and 1.3 mm was examined for 6 weeks in 80 female Sprague-Dawley rats. Seven SCI gradations resulted in three locomotor performance levels measured with BBB (P < 0.01): High: laminectomy (LAM) controls and 0.3 (19.87 +/- 0.35 SEM); Intermediate: 0.5-0.9 (13.71 +/- 0.32); and Low: 1.1-1.3 (9.23 +/- 0.36). Normal paw position was most susceptible to SCI requiring 90% WMS, while consistent plantar stepping was least susceptible depending on 10% WMS. A threshold at the 0.9 severity for coordination, toe clearance, and nearly normal trunk stability and tail usage required 25% WMS. Analysis of interlimb coordination using new phase dispersion (PD) techniques delineated three recovery patterns: synchronous (0.3), modified concordance (0.5, 0.7), and disengaged (0.9, 1.1). Lesion severity correlated to WMS (r(2) = 0.96) and to BBB (r(2) = 0.87) by nonlinear polynomial regressions. Mechanical allodynia developed only after injuries resulting in < or =10% WMS. Nonlinear motor and sensory recovery patterns suggest that small reparative changes may substantially improve function in individuals with SCI. A hierarchical locomotor recovery based on simple segmental versus complex supraspinal motor control is proposed.

Animals↗

PubMed2005

Voluntary wheel running improves recovery from a moderate spinal cord injury.

Recently, locomotor training has been shown to improve overground locomotion in patients with spinal cord injury (SCI). This has triggered renewed interest in the role of exercise in rehabilitation after SCI. However, there are no mouse models for voluntary exercise and recovery of function following SCI. Here, we report voluntary wheel running improves recovery from a SCI in mice. C57Bl/10 female mice received a 60-kdyne T9 contusion injury with an IH impactor after 3 weeks of voluntary wheel running or 3 weeks of standard single housing conditions. Following a 7-day recovery period, running mice were returned to their running wheels. Weekly open-field behavior measured locomotor recovery using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale and the Basso Mouse Scale (BMS) locomotor rating scale, a scale recently developed specifically for mice. Initial experiments using standard rung wheels show that wheel running impaired recovery, but subsequent experiments using a modified flat-surface wheel show improved recovery with exercise. By 14 days post SCI, the modified flat-surface running group had significantly higher BBB and BMS scores than the sedentary group. A repeated measures ANOVA shows locomotor recovery of modified flat-surface running mice was significantly improved compared to sedentary animals (p < 0.05). Locomotor assessment using a ladder beam task also shows a significant improvement in the modified flat-surface runners (p < 0.05). Finally, fibronectin staining shows no significant difference in lesion size between the two groups. These data represent the first mouse model showing voluntary exercise improves recovery after SCI.

Animals↗

PubMed2004

Passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats.

Myelin-reactive T-cells are activated by traumatic spinal cord injury (SCI) in rodents and humans. Despite the historical association of these cells with experimental and clinical neuropathology, recent data suggest a neuroprotective role for myelin-reactive T-cells. Because of the biological and therapeutic implications of these findings, we attempted to reproduce the original neuroprotective vaccine protocols in a model of rat SCI. Specifically, MBP-reactive T-cell function was enhanced in SCI rats via passive or active immunization. Locomotor function was assessed using a standardized locomotor rating scale (Basso-Beattie-Bresnahan scale) and was correlated with myelin and axon sparing. The functional and anatomical integrity of the rubrospinal pathway also was analyzed using the inclined plane test and anatomical tract tracing. MBP-immunized rats exhibited varying degrees of functional impairment, exacerbated lesion pathology, greater rubrospinal neuron loss, increased intraspinal T-cell accumulation, and enhanced macrophage activation relative to SCI control groups. These data are consistent with the conventional view of myelin-reactive T-cells as pathological effector cells.

Animals↗

PubMed2004

Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats.

Spinal cord injury (SCI) induces incapacitating neuropathic pain in the form of allodynia-a painful response to normally non-noxious stimuli. Unfortunately, the underlying mechanisms of these sensory changes are not well understood, and effective treatments for allodynia have proven elusive. We examined whether physical exercise can improve sensory function after experimental SCI by promoting neurotrophin expression in the spinal cord and periphery, which modulates synaptic transmission and function. Female rats with moderate spinal cord contusion participated in treadmill training, swim training, stand training or were untrained. Exercise training began 4 days post surgery, lasted 20-25 min per day, 5 days a week for 7 weeks. Allodynia, as measured using von Frey hairs of different bending forces to the plantar hind paw, developed in the untrained group 3 weeks after SCI. Treadmill training ameliorated allodynia and restored normal sensation by 5 weeks. Swim training had a transient beneficial effect, but allodynia returned by 7 weeks. Stand training had no effect. Resolution of allodynia after treadmill training was associated with normal mRNA levels of brain-derived neurotrophic factor (BDNF) in both the lumbar spinal cord and soleus muscle. No other exercise paradigm restored BDNF centrally and peripherally. Greater recovery from allodynia correlated significantly with the degree of normalization of central and peripheral BDNF levels. These findings suggest that rhythmic, weight-bearing exercise may be an effective intervention to counter SCI-induced allodynia.

Animals↗

PubMed2004

Behavioral testing after spinal cord injury: congruities, complexities, and controversies.

Selection and implementation of behavioral tests in spinal cord injury research is an important process, and yet few papers have focused on these issues. The critical component of any behavioral experiment is the ability to produce reliable, reproducible, and worthwhile data. Unfortunately, the difference between worthwhile and worthless data is often subtle. This paper describes factors that must be considered in order to select the most sensitive behavioral tests to match the hypothesis of the experiment and apply any test in a standardized, consistent manner. Classifications of behavioral tests, their strengths and limitations, as well as methods to overcome these limitations are discussed. Recent work in translating behavioral tests from rats to mice is also provided. The purpose of this article is to provide a framework by which behavioral testing can be standardized within and across spinal cord injury labs.

Animals↗

PubMed2002

Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy.

Lymphocytes respond to myelin proteins after spinal cord injury (SCI) and may contribute to post-traumatic secondary degeneration. However, there is increasing evidence that autoreactive T-lymphocytes may also convey neuroprotection and promote functional recovery after CNS injury. To clarify the role of myelin autoreactive lymphocytes after SCI, we performed contusion injuries in the thoracic spinal cord of transgenic (Tg) mice in which >95% of all CD4+ T-lymphocytes are reactive with myelin basic protein (MBP). We observed significantly impaired recovery of locomotor and reflex function in Tg mice compared with non-Tg (nTg) littermates. Measures of functional impairment in Tg mice correlated with significantly less white matter at the injury site, and morphometric comparisons of injured Tg and nTg spinal cords revealed increased rostrocaudal lesion expansion (i.e., secondary degeneration) in Tg mice. Rostrocaudal to the impact site in SCI-nTg mice, demyelination was restricted to the dorsal funiculus, i.e., axons undergoing Wallerian degeneration. The remaining white matter appeared normal. In contrast, lymphocytes were colocalized with regions of demyelination and axon loss throughout the white matter of SCI-Tg mice. Impaired neurological function and exacerbated neuropathology in SCI-Tg mice were associated with increased intraspinal production of proinflammatory cytokine mRNA; neurotrophin mRNA was not elevated. These data suggest that endogenous MBP-reactive lymphocytes, activated by traumatic SCI, can contribute to tissue injury and impair functional recovery. Any neuroprotection afforded by myelin-reactive T-cells is likely to be an indirect effect mediated by other non-CNS-reactive lymphocytes. Similar to the Tg mice in this study, a subset of humans that are genetically predisposed to autoimmune diseases of the CNS may be adversely affected by vaccine therapies designed to boost autoreactive lymphocyte responses after CNS trauma. Consequently, the safe implementation of such therapies requires that future studies define the mechanisms that control T-cell function within the injured CNS.

Animals↗

PubMed2002

Descending systems contributing to locomotor recovery after mild or moderate spinal cord injury in rats: experimental evidence and a review of literature.

PURPOSE: Locomotor recovery after spinal cord contusion injury (SCI) may be mediated by descending axons spared at the lesion epicenter. Greater axonal sparing is associated with more extensive recovery. Therefore, we identified the source and relative proportion of spared axons associated with extensive or limited locomotor recovery after SCI. METHODS: Female Sprague Dawley rats underwent mild or moderate SCI using the OSU device. RESULTS: Locomotor recovery was greater for the mild than moderate group with the primary differences being restitution of limb coordination, very little toe dragging and minor paw rotation. CONCLUSIONS: The following brain nuclei with substantial neuronal labeling after mild but not moderate SCI may play an important role in locomotor recovery: raphe pallidus and magnus, ventral medullary and pontine reticular formation, lateral vestibular nucleus, red nucleus and locus coeruleus. We review the normal anatomical distribution of descending systems to the lumbar cord in rat and the role they play in motor control.

Animals↗