Analysis of The Sensitivity and Reproducibility Of The Basso, Beattie, Bresnahan (BBB) Scale in Wistar Rats

Filho, Tarcísio Eloy Pessoa de Barros; Molina, Alessandra Eira Iague Sleiman

doi:10.1590/s1807-59322008000100018

Cited by 76 publications

(37 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Like BBB scores (Barros Filho and Molina, 2008; Ferguson et al, 2004; Scheff et al, 2002), mBBB scores are derived from an ordinal scale and are not normally distributed. Therefore, we analyzed mBBB scores using a nonparametric (distribution-free) procedure based on ranks (Conover and Iman, 1981).…”

Section: Methodsmentioning

confidence: 99%

Comparative effects of glibenclamide and riluzole in a rat model of severe cervical spinal cord injury

Simard

Tsymbalyuk

Keledjian

et al. 2012

Experimental Neurology

107

View full text Add to dashboard Cite

Both glibenclamide and riluzole reduce necrosis and improve outcome in rat models of spinal cord injury (SCI). In SCI, gene suppression experiments show that newly upregulated sulfonylurea receptor 1 (Sur1)-regulated NCCa- ATP channels in microvascular endothelial cells are responsible for “persistent sodium currents” that cause capillary fragmentation and “progressive hemorrhagic necrosis”. Glibenclamide is a potent blocker of Sur1-regulated NCCa-ATP channels (IC50,6–48 nM). Riluzole is a pleotropic drug that blocks “persistent sodium currents” in neurons, but in SCI, its molecular mechanism of action is uncertain. We hypothesized that riluzole might block the putative pore-forming subunits of Sur1-regulated NCCa-ATP channels, Trpm4. In patch clamp experiments, riluzole blocked Sur1-regulated NCCa-ATP channels in endothelial cells and heterologously expressed Trpm4 (IC50,31 μM). Using a rat model of cervical SCI associated with high mortality, we compared the effects of glibenclamide and riluzole administered beginning at 3 h and continuing for 7 days after impact. During the acute phase, both drugs reduced capillary fragmentation and progressive hemorrhagic necrosis, and both prevented death. At 6 weeks, modified (unilateral) Basso, Beattie, Bresnahan locomotor scores were similar, but measures of complex function (grip strength, rearing, accelerating rotarod) and tissue sparing were significantly better with glibenclamide than with riluzole. We conclude that both drugs act similarly, glibenclamide on the regulatory subunit, and riluzole on the putative pore-forming subunit of the Sur1-regulated NCCa-ATP channel. Differences in specificity, dose-limiting potency, or in spectrum of action may account for the apparent superiority of glibenclamide over riluzole in this model of severe SCI.

show abstract

Section: Methodsmentioning

confidence: 99%

Comparative effects of glibenclamide and riluzole in a rat model of severe cervical spinal cord injury

Simard

Tsymbalyuk

Keledjian

et al. 2012

Experimental Neurology

107

View full text Add to dashboard Cite

show abstract

“…These initial results emphasized the beneficial effects of mild cooling on white matter integrity and long tract function. Most hypothermia studies have however relied on the open field behavioral test, which may be subjective and highly variable in many types of SCI [40]. Moreover, BBB testing while assessing locomotor activity does not necessarily correlate with the functional integrity and neurological conduction of the spinal cord.…”

Section: Resultsmentioning

confidence: 99%

Potential long-term benefits of acute hypothermia after spinal cord injury

Maybhate

Bazley

et al. 2012

Critical Care Medicine

View full text Add to dashboard Cite

Objective Neuroprotection by hypothermia has been an important research topic over last two decades. In animal models of spinal cord injury (SCI), the primary focus has been assessing effects of hypothermia on behavioral and histological outcomes. While a few studies have investigated electrophysiological changes in descending motor pathways with motor evoked potentials recorded during cooling, we report here, hypothermia induced increased electrical conduction in the ascending spinal cord pathways with somatosensory evoked potentials (SSEPs) in injured rats. In our experiments these effects lasted long after the acute hypothermia and were accompanied with potential long term improvements in motor movement. Design Laboratory Investigation. Setting University Medical School. Subjects 21 Female Lewis Rats. Interventions Hypothermia. Measurements and Main Results All animals underwent spinal cord contusion, with the NYU-Impactor, by a 12.5mm weight drop at thoracic vertebra T8. A group (n=10) was randomly assigned for a systemic 2hr. hypothermia episode (32±0.5°C) initiated ~2.0hrs post-injury. 11 rats were controls with post-injury temperature maintained at 37±0.5°C for 2hrs. The two groups underwent pre-injury, weekly post-injury (up to 4wks) SSEP recordings and standard motor behavioral tests (BBB). Three randomly selected rats from each group were euthanized for histological analysis at post-injury Day 3 and Day 28. Compared to controls, the hypothermia group showed significantly higher SSEP amplitudes post-injury; with longer latencies. The BBB scores were also higher immediately after injury and 4 weeks later in the hypothermia group. Importantly, specific changes in the BBB scores in hypothermia group (not seen in controls) indicated regained functions critical for motor control. Histological evaluations showed more tissue preservation in hypothermia group. Conclusions Post-SCI, early systemic hypothermia provided significant neuroprotection weeks after injury via improved sensory electrophysiological signals in rats. This was accompanied by higher motor behavioral scores and more spared tissue in acute and post-acute periods after injury.

show abstract

“…Like BBB scores (Scheff et al, 2002; Ferguson et al, 2004; Barros Filho and Molina, 2008), mBBB scores are derived from an ordinal scale and are not normally distributed. Therefore, we analyzed mBBB scores using a nonparametric (distribution-free) procedure based on ranks (Conover and Iman, 1981).…”

Section: Methodsmentioning

confidence: 99%

Spinal cord injury with unilateral versus bilateral primary hemorrhage — Effects of glibenclamide

Simard

Popovich

Tsymbalyuk

et al. 2012

Experimental Neurology

View full text Add to dashboard Cite

In spinal cord injury (SCI), block of Sur1-regulated NCCa-ATP channels by glibenclamide protects penumbral capillaries from delayed fragmentation, resulting in reduced secondary hemorrhage, smaller lesions and better neurological function. All published experiments demonstrating a beneficial effect of glibenclamide in rat models of SCI have used a cervical hemicord impact calibrated to produce primary hemorrhage located exclusively ipsilateral to the site of impact. Here, we tested the hypothesis that glibenclamide also would be protective in a model with more extensive, bilateral primary hemorrhage. We studied the effect of glibenclamide in 2 rat cervical hemicord contusion models with identical impact force (10 g, 25 mm), one with the impactor positioned laterally to yield unilateral primary hemorrhage (UPH), and the other with the impactor positioned more medially, yielding larger, bilateral primary hemorrhages (BPH) and 6-week lesion volumes that were 45% larger. Functional outcome measures included: modified (unilateral) Basso, Beattie, and Bresnahan scores, angled plane performance, and rearing times. In the UPH model, the effects of glibenclamide were similar to previous observations, including a functional benefit as early as 24 h after injury and 6-week lesion volumes that were 57% smaller than controls. In the BPH model, glibenclamide exerted a significant benefit over controls, but the functional benefit was smaller than in the UPH model and 6-week lesion volumes were 33% smaller than controls. We conclude that glibenclamide is beneficial in different models of cervical SCI, with the magnitude of the benefit depending on the magnitude and extent of primary hemorrhage.

show abstract

Analysis of The Sensitivity and Reproducibility Of The Basso, Beattie, Bresnahan (BBB) Scale in Wistar Rats

Cited by 76 publications

References 19 publications

Comparative effects of glibenclamide and riluzole in a rat model of severe cervical spinal cord injury

Comparative effects of glibenclamide and riluzole in a rat model of severe cervical spinal cord injury

Potential long-term benefits of acute hypothermia after spinal cord injury

Spinal cord injury with unilateral versus bilateral primary hemorrhage — Effects of glibenclamide

Contact Info

Product

Resources

About