Motor neuronal and glial apoptosis in the adult facial nucleus after intracranial nerve transection.
OBJECTIVE
Intracranial lesions affecting the facial nerve are usually associated with significant morbidity and poor functional restitution, despite the fact that a peripheral nerve injury normally recovers well. Mechanistic explanations are needed to direct future therapies. Although neonatal motor neurons are known to die as a result of apoptosis after axotomy, this cell death mechanism has not been explicitly demonstrated after peripheral cranial nerve transection in adult mammals.


METHODS
The authors induced substantial retrograde neuronal death in the adult rodent by transecting the facial nerve during its intracranial course. Neuronal apoptosis was demonstrated as shrunken facial motor neurons, retrogradely labeled with fluorogold and with nuclei positively labeled by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). Glial apoptosis was demonstrated by double labeling with respect to cell type. On postinjury Days 7 and 14, the intracranial axotomy led to neuronal apoptosis, corresponding to a neuronal loss that was observed quantitatively in cresyl violet-stained tissue sections obtained using a stereological method. In contrast, no neuronal apoptosis was observed after creating a distal lesion of the facial nerve, which causes less neuronal loss. In addition, glial apoptosis was seen in the facial nucleus after both distal and proximal axotomy. Whereas the proximal intracranial axotomy led to TUNEL-positive nuclei in cells showing markers for oligodendrocytes and microglia, only the latter glial cell population was double labeled with TUNEL-positive nuclei after distal lesioning.


CONCLUSIONS
These findings may ultimately lead to new therapeutic strategies in patients suffering from facial nerve palsy due to an intracranial lesion.
Mattsson
Per
P
Department of Clinical Neuroscience (Section for Neurosurgery), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. mattsson@karolinska.se
Delfani
Kioumars
K
Janson
Ann Marie
AM
Svensson
Mikael
M
D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D005154:Facial Nerve / Q000601:surgery*; D020220:Facial Nerve Injuries / Q000150:complications*; D020287:In Situ Nick-End Labeling; D008297:Male; D009046:Motor Neurons / Q000473:pathology*; D009457:Neuroglia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley