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TiO2-Nanowired Delivery of DL-3-n-butylphthalide (DL-NBP) Attenuates Blood-Brain Barrier Disruption, Brain Edema Formation, and Neuronal Damages Following Concussive Head Injury
Bethune Int Peace Hosp, Dept Neurol, Zhongshan Rd West, Shijiazhuang, Hebei, Peoples R China..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
CSPC NBP Pharmaceut Med, Zhongshan Rd West, Shijiazhuang, Hebei, Peoples R China..
CSPC NBP Pharmaceut Med, Zhongshan Rd West, Shijiazhuang, Hebei, Peoples R China..
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 350-358Article in journal (Refereed) Published
Abstract [en]

DL-3-n-butylphthalide (DL-NBP) is one of the constituents of Chinese celery extract that is used to treat stroke, dementia, and ischemic diseases. However, its role in traumatic brain injury is less well known. In this investigation, neuroprotective effects of DL-NBP in concussive head injury (CHI) on brain pathology were explored in a rat model. CHI was inflicted in anesthetized rats by dropping a weight of 114.6 g from a height of 20 cm through a guide tube on the exposed right parietal bone inducing an impact of 0.224 N and allowed them to survive 4 to 24 h after the primary insult. DL-NBP was administered (40 or 60 mg/kg, i.p.) 2 and 4 h after injury in 8-h survival group and 8 and 12 h after trauma in 24-h survival group. In addition, TiO2-nanowired delivery of DL-NBP (20 or 40 mg/kg, i.p.) in 8 and 24 h CHI rats was also examined. Untreated CHI showed a progressive increase in blood-brain barrier (BBB) breakdown to Evans blue albumin (EBA) and radioiodine (I[131]-), edema formation, and neuronal injuries. The magnitude and intensity of these pathological changes were most marked in the left hemisphere. Treatment with DL-NBP significantly reduced brain pathology in CHI following 8 to 12 h at 40-mg dose. However, 60-mg dose is needed to thwart brain pathology at 24 h following CHI. On the other hand, TiO2-DL-NBP was effective in reducing brain damage up to 8 or 12 h using a 20-mg dose and only 40-mg dose was needed for neuroprotection in CHI at 24 h. These observations are the first to suggest that (i) DL-NBP is quite effective in reducing brain pathology and (ii) nanodelivery of DL-NBP has far more superior effects in CHI, not reported earlier.

Place, publisher, year, edition, pages
Humana Press, 2018. Vol. 55, no 1, p. 350-358
Keywords [en]
DL-3-n-butylphthalide (DL-NBP), Concussive head injury (CHI), Blood-brain barrier, Brain edema, Neuronal injury, TiO2 nanodelivery, Neuroprotection
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-346905DOI: 10.1007/s12035-017-0746-5ISI: 000424702600034PubMedID: 28856586OAI: oai:DiVA.org:uu-346905DiVA, id: diva2:1192567
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved

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Sharma, ArunaSharma, Hari Shanker

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