Ketone Esters Partially and Selectively Rescue Mitochondrial Bioenergetics After Acute Cervical Spinal Cord Injury in...

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Spinal cord injury (SCI) involves primary damage and secondary injury cascades.
• Secondary injury is characterized by metabolic dysregulation and impaired mitochondrial bioenergetics.
• Ketosis has shown promise in mitigating secondary neuropathology by reducing oxidative stress and inflammation.

Purpose of the Study:

• To investigate the effects of an exogenous ketone monoester (KE) on mitochondrial function following SCI.
• To evaluate KE as an alternative to ketogenic diets for ameliorating metabolic deficits post-SCI.
• To assess the temporal effects of KE on mitochondrial bioenergetics between 1 and 14 days post-injury.

Main Methods:

• Cervical level 5 (C5) hemi-contusion SCI model in animals.
• Administration of a standard diet (SD) or a ketone ester diet (KED) with oral KE (OKE).
• Assessment of mitochondrial function and electron transport chain (ETC) component expression at various time points post-SCI.

Main Results:

• Mitochondrial function was significantly reduced after SCI, with decreased ETC component expression.
• KE partially rescued bioenergetic parameters at 1 day post-SCI (BHB ~2 mM).
• Most significant neuroprotective effects were observed at 14 days post-SCI, with higher BHB concentrations (4-6 mM).

Conclusions:

• This study is the first to demonstrate KE's efficacy in restoring mitochondrial function after SCI.
• KE administration effectively ameliorates metabolic dysregulation post-traumatic SCI.
• KE offers a viable, non-restrictive dietary strategy for neuroprotection following SCI.