Open AccessAcute intrathecal BDNF enhances functional recovery after cervical spinal cord injury in rats
Author(s) -
Gary C. Sieck,
Heather M. Gransee,
Wen Zhi Zhan,
Carlos B. Mantilla
Publication year - 2021
Publication title -
journal of neurophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.302
H-Index - 245
eISSN - 1522-1598
pISSN - 0022-3077
DOI - 10.1152/jn.00146.2021
Subject(s) - medicine , spinal cord , anesthesia , hypercapnia , spinal cord injury , neuroplasticity , neurotrophic factors , excitatory postsynaptic potential , electromyography , premovement neuronal activity , neuroscience , psychology , physical medicine and rehabilitation , acidosis , receptor , psychiatry
Unilateral C 2 hemisection (C 2 SH) disrupts descending inspiratory-related drive to phrenic motor neurons and thus, silences rhythmic diaphragm muscle (DIAm) activity. There is gradual recovery of rhythmic DIAm EMG activity over time post-C 2 SH, consistent with neuroplasticity, which is enhanced by chronic (2 wk) intrathecal BDNF treatment. In the present study, we hypothesized that acute (30 min) intrathecal BDNF treatment also enhances recovery of DIAm EMG activity after C 2 SH. Rats were implanted with bilateral DIAm EMG electrodes to verify the absence of ipsilateral eupneic DIAm EMG activity at the time of C 2 SH and at 3 days post-C 2 SH. In those animals displaying no recovery of DIAm EMG activity after 28 days ( n = 7), BDNF was administered intrathecally (450 mcg) at C 4 . DIAm EMG activity was measured continuously both before and for 30 min after BDNF treatment, during eupnea, hypoxia-hypercapnia, and spontaneous sighs. Acute BDNF treatment restored eupneic DIAm EMG activity in all treated animals to an amplitude that was 78% ± 9% of pre-C 2 SH root mean square (RMS) ( P < 0.001). In addition, acute BDNF treatment increased DIAm RMS EMG amplitude during hypoxia-hypercapnia ( P = 0.023) but had no effect on RMS EMG amplitude during sighs. These results support an acute modulatory role of BDNF signaling on excitatory synaptic transmission at phrenic motor neurons after cervical spinal cord injury. NEW & NOTEWORTHY Brain-derived neurotrophic factor (BDNF) plays an important role in promoting neuroplasticity following unilateral C 2 spinal hemisection (C 2 SH). BDNF was administered intrathecally in rats displaying lack of ipsilateral inspiratory-related diaphragm (DIAm) EMG activity after C 2 SH. Acute BDNF treatment (30 min) restored eupneic DIAm EMG activity in all treated animals to 78% ± 9% of pre-C 2 SH level. In addition, acute BDNF treatment increased DIAm EMG amplitude during hypoxia-hypercapnia but had no effect on EMG amplitude during sighs.