TY - CHAP
T1 - Cerebrolysin enhances spinal cord conduction and reduces blood-spinal cord barrier breakdown, edema formation, immediate early gene expression and cord pathology after injury
AU - Sahib, Seaab
AU - Sharma, Aruna
AU - Menon, Preeti K.
AU - Muresanu, Dafin F.
AU - Castellani, Rudy J.
AU - Nozari, Ala
AU - Lafuente, José Vicente
AU - Bryukhovetskiy, Igor
AU - Tian, Z. Ryan
AU - Patnaik, Ranjana
AU - Buzoianu, Anca D.
AU - Wiklund, Lars
AU - Sharma, Hari Shanker
N1 - Funding Information:
This investigation is supported by grants from the Air Force Office of Scientific Research (EOARD, London, UK), and Air Force Material Command, USAF, under grant number FA8655-05-1-3065; Grants from the Alzheimer's Association (IIRG-09- 132087), the National Institutes of Health (R01 AG028679) and the Dr. Robert M. Kohrman Memorial Fund (RJC); Swedish Medical Research Council (Nr 2710-HSS), Göran Gustafsson Foundation, Stockholm, Sweden (HSS), Astra Zeneca, Mölndal, Sweden (HSS/AS), Alexander von Humboldt Foundation, Bonn, Germany (HSS), The University Grants Commission, New Delhi, India (HSS/AS), Ministry of Science & Technology, Govt. of India (HSS/AS), Indian Medical Research Council, New Delhi, India (HSS/AS) and India-EU Co-operation Program (RP/AS/HSS) and IT-901/16 (JVL), Government of Basque Country and PPG 17/51 (JVL), JVL thanks to the support of the University of the Basque Country (UPV/EHU) PPG 17/51 and 14/08, the Basque Government (IT-901/16 and CS-2203) Basque Country, Spain; and Foundation for Nanoneuroscience and Nanoneuroprotection (FSNN), Romania. Technical assistance of Kärstin Flink, Ingmarie Olsson, Uppsala University and Franzisca Drum, Katja Deparade, Free University Berlin, Germany are highly appreciated. Technical and human support provided by Dr. Ricardo Andrade from SGIker (UPV/EHU) is gratefully acknowledged. Dr. Seaab Sahib is supported by Research Fellowship at the University of Arkansas Fayetteville AR by Department of Community Health; Middle Technical University; Wassit; Iraq, and The Higher Committee for Education Development in Iraq; Baghdad; Iraq. We thank Suraj Sharma, Blekinge Inst. Technology, Karlskrona, Sweden, and Dr. Saja Alshafeay, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq for computer and graphic support. We deeply appreciate Dr. Tomas Winkler and Professor Erik Stålberg (Uppsala University Hospital, Department of Clinical Neurophysiology) for his support and help in the Spinal cord evoke potential Research. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the Air Force Office of Scientific Research or the U.S. Government.
Funding Information:
This investigation is supported by grants from the Air Force Office of Scientific Research (EOARD, London, UK), and Air Force Material Command, USAF, under grant number FA8655-05-1-3065; Grants from the Alzheimer's Association (IIRG-09- 132087), the National Institutes of Health (R01 AG028679) and the Dr. Robert M. Kohrman Memorial Fund (RJC); Swedish Medical Research Council (Nr 2710-HSS), G?ran Gustafsson Foundation, Stockholm, Sweden (HSS), Astra Zeneca, M?lndal, Sweden (HSS/AS), Alexander von Humboldt Foundation, Bonn, Germany (HSS), The University Grants Commission, New Delhi, India (HSS/AS), Ministry of Science & Technology, Govt. of India (HSS/AS), Indian Medical Research Council, New Delhi, India (HSS/AS) and India-EU Co-operation Program (RP/AS/HSS) and IT-901/16 (JVL), Government of Basque Country and PPG 17/51 (JVL), JVL thanks to the support of the University of the Basque Country (UPV/EHU) PPG 17/51 and 14/08, the Basque Government (IT-901/16 and CS-2203) Basque Country, Spain; and Foundation for Nanoneuroscience and Nanoneuroprotection (FSNN), Romania. Technical assistance of K?rstin Flink, Ingmarie Olsson, Uppsala University and Franzisca Drum, Katja Deparade, Free University Berlin, Germany are highly appreciated. Technical and human support provided by Dr. Ricardo Andrade from SGIker (UPV/EHU) is gratefully acknowledged. Dr. Seaab Sahib is supported by Research Fellowship at the University of Arkansas Fayetteville AR by Department of Community Health; Middle Technical University; Wassit; Iraq, and The Higher Committee for Education Development in Iraq; Baghdad; Iraq. We thank Suraj Sharma, Blekinge Inst. Technology, Karlskrona, Sweden, and Dr. Saja Alshafeay, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq for computer and graphic support. We deeply appreciate Dr. Tomas Winkler and Professor Erik St?lberg (Uppsala University Hospital, Department of Clinical Neurophysiology) for his support and help in the Spinal cord evoke potential Research. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the Air Force Office of Scientific Research or the U.S. Government. The authors have no conflict of interests with any funding agency or entity reported here.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/1
Y1 - 2020/1
N2 - Spinal cord evoked potentials (SCEP) are good indicators of spinal cord function in health and disease. Disturbances in SCEP amplitudes and latencies during spinal cord monitoring predict spinal cord pathology following trauma. Treatment with neuroprotective agents preserves SCEP and reduces cord pathology after injury. The possibility that cerebrolysin, a balanced composition of neurotrophic factors improves spinal cord conduction, attenuates blood-spinal cord barrier (BSCB) disruption, edema formation, and cord pathology was examined in spinal cord injury (SCI). SCEP is recorded from epidural space over rat spinal cord T9 and T12 segments after peripheral nerves stimulation. SCEP consists of a small positive peak (MPP), followed by a prominent negative peak (MNP) that is stable before SCI. A longitudinal incision (2 mm deep and 5 mm long) into the right dorsal horn (T10 and T11 segments) resulted in an immediate long-lasting depression of the rostral MNP with an increase in the latencies. Pretreatment with either cerebrolysin (CBL 5 mL/kg, i.v. 30 min before) alone or TiO2 nanowired delivery of cerebrolysin (NWCBL 2.5 mL/kg, i.v.) prevented the loss of MNP amplitude and even enhanced further from the pre-injury level after SCI without affecting latencies. At 5 h, SCI induced edema, BSCB breakdown, and cell injuries were significantly reduced by CBL and NWCBL pretreatment. Interestingly this effect on SCEP and cord pathology was still prominent when the NWCBL was delivered 2 min after SCI. Moreover, expressions of c-fos and c-jun genes that are prominent at 5 h in untreated SCI are also considerably reduced by CBL and NWCBL treatment. These results are the first to show that CBL and NWCBL enhanced SCEP activity and thwarted the development of cord pathology after SCI. Furthermore, NWCBL in low doses has superior neuroprotective effects on SCEP and cord pathology, not reported earlier. The functional significance and future clinical potential of CBL and NWCBL in SCI are discussed.
AB - Spinal cord evoked potentials (SCEP) are good indicators of spinal cord function in health and disease. Disturbances in SCEP amplitudes and latencies during spinal cord monitoring predict spinal cord pathology following trauma. Treatment with neuroprotective agents preserves SCEP and reduces cord pathology after injury. The possibility that cerebrolysin, a balanced composition of neurotrophic factors improves spinal cord conduction, attenuates blood-spinal cord barrier (BSCB) disruption, edema formation, and cord pathology was examined in spinal cord injury (SCI). SCEP is recorded from epidural space over rat spinal cord T9 and T12 segments after peripheral nerves stimulation. SCEP consists of a small positive peak (MPP), followed by a prominent negative peak (MNP) that is stable before SCI. A longitudinal incision (2 mm deep and 5 mm long) into the right dorsal horn (T10 and T11 segments) resulted in an immediate long-lasting depression of the rostral MNP with an increase in the latencies. Pretreatment with either cerebrolysin (CBL 5 mL/kg, i.v. 30 min before) alone or TiO2 nanowired delivery of cerebrolysin (NWCBL 2.5 mL/kg, i.v.) prevented the loss of MNP amplitude and even enhanced further from the pre-injury level after SCI without affecting latencies. At 5 h, SCI induced edema, BSCB breakdown, and cell injuries were significantly reduced by CBL and NWCBL pretreatment. Interestingly this effect on SCEP and cord pathology was still prominent when the NWCBL was delivered 2 min after SCI. Moreover, expressions of c-fos and c-jun genes that are prominent at 5 h in untreated SCI are also considerably reduced by CBL and NWCBL treatment. These results are the first to show that CBL and NWCBL enhanced SCEP activity and thwarted the development of cord pathology after SCI. Furthermore, NWCBL in low doses has superior neuroprotective effects on SCEP and cord pathology, not reported earlier. The functional significance and future clinical potential of CBL and NWCBL in SCI are discussed.
KW - Blood-spinal cord barrier
KW - Cerebrolysin
KW - Gene expression
KW - Neuroprotection
KW - Spinal cord edema
KW - Spinal cord evoked potential
KW - Spinal cord injury
KW - TiO nanowired delivery
UR - http://www.scopus.com/inward/record.url?scp=85095999446&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095999446&partnerID=8YFLogxK
U2 - 10.1016/bs.pbr.2020.09.012
DO - 10.1016/bs.pbr.2020.09.012
M3 - Chapter
C2 - 33223040
AN - SCOPUS:85095999446
SN - 9780128208137
T3 - Progress in Brain Research
SP - 397
EP - 438
BT - Neuropharmacology of Neuroprotection
A2 - Sharma, Hari Shanker
A2 - Sharma, Aruna
PB - Elsevier B.V.
ER -