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function of the gastrocnemius and soleus muscles following   determined by its effect on the injured nerve stump and
          denervation. The sensory‑protected group underwent   secondarily by its effect on the muscle.  Other studies
                                                                                                 [29]
          saphenous‑to‑tibial nerve transfer using end‑to‑end repair.   have not largely substantiated these claims.
          Compared to the unprotected group, gross and histological   End‑to‑side neurorrhaphy
          examination showed the sensory‑protected group had   End‑to‑side  neurorrhaphy provides  trophic support from
          higher muscle  weight and greater preservation of muscle   the donor nerve and enables the regenerated motor axons
          structure, including less fiber atrophy and connective   to reach their target, thus bypassing the need for a second
          tissue hyperplasia. More importantly, the sensory‑protected   operation to replace the motor nerve supply. In contrast,
          rats demonstrated larger maximum compound action    end‑to‑end neurorrhaphy requires cutting the donor
          potentials  and  relative  preservation  of  isometric  force   sensory nerve and suturing  it to its  native stump once
                  [9]
          overtime.  Follow‑up studies showed sensory protection   the motor nerve has regenerated, essentially denervating
                                              [23]
          also prevented muscle spindle deterioration.  Nonetheless,   the muscle twice. Studies have shown that two cycles
          rats that underwent immediate nerve repair had the best   of denervation and reinnervation lead to suboptimal
          structural and functional outcomes.
                                                              functional recovery,  as demonstrated by reduced muscle
          The benefits of sensory protection have been        power and force. [31]
          substantiated  by  other  groups. [24‑26]   Common  outcomes   End‑to‑side coaptation is a compelling alternative
          of end‑to‑end  sensory  nerve  grafting  in  the  lower limbs   when conventional end‑to‑end coaptation is not
          include  preservation of fiber distribution, maintenance   practical. Such cases occur when the transected end
          of motor endplates, and less muscle atrophy, fibrosis,   of  the  motor  nerve  stump  is  far  from  its  muscle
          collagenization,  and fat  deposition. [16,25]   Consistent  with   target or when there are multiple denervated muscles.
          lower extremity studies,  Beck‑Broichsitter et  al.  found   Zuijdendorp  et  al.  recently investigated the efficacy
                                                   [11]
                                                                              [32]
          that sensory‑protection in the upper extremity  resulted   of sensory protection using end‑to‑side neurorrhaphy.
          in  higher  muscle  weight,  larger  axon  diameter,  and   The investigators sutured the divided end of the sural
          larger nerve fiber surface area. However,  there was no   nerve to the lateral aspect of the tibial nerve stump
          definitive  difference in grasping  strength  between  the   and  examined the gastrocnemius  muscle  at 5  weeks
          sensory‑protected and unprotected groups. [11]
                                                              and 10  weeks postoperatively. Compared to primary
          The protective effect by a purely sensory nerve can be   end‑to‑end neurorrhaphy, the sensory‑protected group
          explained by a number of factors. First, the trophic effect   demonstrated a statistically significant increase in muscle
          of the sensory nerve provides a supportive milieu for the   weight and decrease in muscle atrophy compared to the
          maintenance of skeletal muscles. More specifically, sensory   unprotected group.  Despite the ongoing debate over
                                                                               [32]
          protection  modulates  the  expression  of  both  glial  cell   the efficacy, end‑to‑side neurorrhaphy remains a viable
          line‑derived neurotrophic factor  (GDNF) and brain‑derived   approach that requires further investigation.
          neurotrophic factor  (BDNF), thereby optimizing the   Researchers have also used the end‑to‑side neurorrhaphy
          environment for muscle preservation and reinnervation. [12,27]    model to study the protective effects of mixed nerve
          Second, the sensory nerve helps maintain the architecture   containing both motor and sensory axons. The use of
          of the residual nerve stump and basal lamina of endoneurial   mixed nerve is supported by a recent study by Li et al.
                                                                                                             [33]
          tubes, thus facilitating later access by regenerating motor   who compared muscle protection following  denervation
          axons. [4,28]  Third, Schwann cells of the distal stump switch   using the peroneal nerve (mixed protection) or sural
          from a myelinating phenotype to a growth‑supporting   nerve  (sensory  protection).  They showed  that both the
          phenotype  by  upregulating  specific  genes  associated  with   mixed‑ and sensory‑protected groups demonstrated
          regeneration.  These trophic effects help maintain a   preservation of muscle architecture and better functional
                     [19]
          growth‑supportive environment, which would otherwise   recovery following reinnervation compared to the
          deteriorate with time.
                                                              unprotected group. Further, the investigators showed
          Although  the  research overwhelmingly  supports the   that mixed protection was superior to sensory protection
          benefits  of sensory  protection,  it  is  important  to   in terms of axon structure (more regenerated myelinated
          recognize points of contention. Sulaiman  et  al.    axons, larger axonal diameter, thicker myelin sheath) and
                                                         [29]
          proposed that  the  presence  of  sensory  nerves  instead   function (greater contraction force).  They controlled
                                                                                              [33]
          create  an unfavorable environment  that reduces motor   for stump reinnervation by the motor component of
          axonal regeneration and myelination  of regenerated   the mixed nerve by performing end‑to‑side coaptation
          axons. The authors advocated that sensory nerves actively   and capping the end of the transected motor nerve. In
          inhibit  motor axonal regeneration  by  not only physically   contrast, another study by Michalski  et  al.  reported
                                                                                                     [27]
          occupying the  endoneurial  pathways,  but  by  altering   no difference between mixed‑ and sensory‑protected
          Schwann cells  in the distal nerve stump. Specifically,   groups  in  terms  of  number  of  regenerating  axons,  axon
          sensory nerves shift Schwann cells  toward a phenotype   diameter,  and  myelin  cross‑sectional  area  in  the  distal
          that is  less receptive to regenerating  motor axons, in   stump. However, there was a difference in the expression
          part by down‑regulating the expression of L2/HNK‑1   of denervation‑induced GDNF, and BDNF expression
          required for interaction between Schwann cells and motor   between the two groups, which suggests that the main
          axons. [29,30]  Furthermore, the investigators  argue that the   benefit of mixed protection is more rapid normalization
          functional outcome of chronic denervation is primarily   of trophic factors.
           204                                                           Plast Aesthet Res || Vol 2 || Issue 4 || Jul 15, 2015
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