| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Research Abstract |
Object : Cerebral palsy (CP) arises in the early stages of brain development and manifests as spastic paresis that is often associated with cognitive dysfunction. Available treatments for CP, including rehabilitation, botulinum toxin, selective dorsal rhizotomy, and intrathecal baclofen (ITB), are used for the management of spasticity and do not affect motor weakness or higher cerebral function. In this study, we investigated whether the management of spasticity using ITB can also affect motor function, whether improvement in motor ability by the use of ITB is associated with histological recovery of the damaged brain, and whether the release of spasticity is associated with an improvement in intellectual function.
Methods : Sprague-Dawley rats were placed into 4 groups : control, CP model, and CP model with either early or late ITB therapy. For the CP model, rats on postnatal day 7 (P7) were placed under hypoxic conditions (8% O_2) for 150 min after ligation of the right common carotid
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artery. In the ITB therapy groups, a spinal catheter was connected to an osmotic pump filled with baclofen and placed in the spinal subarachnoid space on P21 (early) or P35 (late). A daily dose of 12μg of baclofen was continuously administered until P49, resulting in 28 or 14 days of therapy. Changes in spasticity in the CP and CP with ITB treatment groups were confirmed using an evoked potential in the planter muscle.
Results : In the CP group, the time required to complete a beam walking test on P49 was significantly increased compared with that in the control group (4.09±0.18 sec vs. 2.10±0.13 sec in the control group). This was normalized to 2.26±0.16 sec (early) and 2.52±0.15 sec (late) in the ITB treatment groups. Radial arm maze performance on P49 indicated that spatial reference memory had deteriorated in the CP group (0.85±0.34 points vs. 2.27±0.35 points in the control group), and working memory was also decreased upon induction of CP (0.14±0.18 points vs. 0.64±0.30 points in the control group). These functions did not recover after ITB treatment. On P49, the thickness of the corpus callosum decreased to 147.9±24.6μm in the CP group ; this was significantly lesser than that in the control group (446.1±22.1μm). The corpus callosum was not restored by ITB treatment.
Conclusions : Management of spasticity using ITB therapy improved walking ability in a rat CP model. This improvement was not due to structural regeneration of the damaged brain but due to functional compensation or adaptation. ITB reduces harmful sensory and motor stimulation caused by spasticity to more optimal levels ; this contributes to the recovery of motor function. However, the effect of ITB was not sufficient for intellectual recovery in the rat CP model. Less
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