Facial Nerve Recovery in KbDb and C1q Knockout Mice: A Role for Histocompatibility Complex 1

Abstract

Background: Understanding the mechanisms in nerve damage can lead to better outcomes for neuronal rehabilitation. The purpose of our study was to assess the effect of major histocompatibility complex I deficiency and inhibition of the classical complement pathway (C1q) on functional recovery and cell survival in the facial motor nucleus (FMN) after crush injury in adult and juvenile mice.

Methods: A prospective blinded analysis of functional recovery and cell survival in the FMN after a unilateral facial nerve crush injury in juvenile and adult mice was undertaken between wild-type, C1q knockout (C1q-/-), and KbDb knockout (KbDb-/-) groups. Whisker function was quantified to assess functional recovery. Neuron counts were performed to determine neuron survival in the FMN after recovery.

Results: After facial nerve injury, all adult wild-type mice fully recovered. Juvenile mice recovered incompletely corresponding to a greater neuron loss in the FMN of juveniles compared with adults. The C1q-/- juvenile and adult groups did not differ from wild type. The KbDb-/- adults demonstrated 50% recovery of whisker movement and decreased cell survival in FMN. The KbDb-/- juvenile group did not demonstrate any difference from control group.

Conclusion: Histocompatibility complex I plays a role for neuroprotection and enhanced facial nerve recovery in adult mice. Inhibition of the classical complement pathway alone does not affect functional recovery or neuronal survival. The alternative and mannose binding pathways pose alternative means for activating the final components of the pathway that may lead to acute nerve damage.

Fig. 1.

Orientation of the mouse head is estimated by performing linear regression on each side of the facial contour.

Fig. 2.

A, The selected whisker is detected via application of the Sobel operator and the Hough transform within the region of interest. B, Using the location and the orientation of the detected whisker, an elliptical mask is created. C, The elliptical mask is applied to the subsequent frame. D, The selected whisker shown in the subsequent frame is detected.

Fig. 3.

Functional recovery in juvenile and adult KbDb−/− mice. A, Both wild-type (WT) and KbDb−/− juvenile mice demonstrate incomplete recovery of whisker function after crush injury. B, Adult WT mice demonstrate consistent recovery of whisker function by postinjury day 13, whereas KbDb−/− mice demonstrate incomplete recovery during the same time period (*P < 0.05).

Fig. 4.

Comparison of FMN neuron number in adult and juvenile KbDb−/− mice after facial nerve crush injury. Facial motor neuron numbers were determined as in Methods. The percent loss was calculated using the contralateral side as control. Both juvenile and adult mice KbDb−/− demonstrated decreased FMN number compared with wild-type (WT) after crush injury (*P < 0.05).

Fig. 5.

Functional recovery in juvenile and adult C1q−/− mice. A, Both wild-type (WT) and C1q−/− juvenile mice demonstrate incomplete recovery of whisker function after crush injury. B, Both WT and C1q−/− adult mice demonstrate similar recovery of whisker function after crush injury, excepting as noted on postinjury day 13 (*P < 0.05).

Fig. 6.

Comparison of FMN neuron number in adult and juvenile C1q−/− mice after facial nerve crush injury. Facial motor neuron numbers were determined as in Methods. The percent loss was calculated using the contralateral side as control. Neither juvenile nor adult C1q−/− mice demonstrated decreased FMN number compared with wild-type (WT) after crush injury.