Peroneal Functional Index Research Articles

Criteria for assessing peripheral nerve injury. Behavioral and functional assessment in non-operated Wistar rats.

PurposeTo evaluate the normality pattern in functional tests of peripheral nerves.MethodsSixty female and sixty male Wistar rats were submitted to vibrissae movement and nictitating reflex for facial nerve; grooming test and grasping test for brachial plexus; and walking tracking test and horizontal ladder test for lumbar plexus. The tests were performed separately, with an interval of seven days between each.ResultsAll animals showed the best score in vibrissae movement, nictitating reflex, grooming test, and horizontal ladder test. The best score was acquired for the first time in more than 90% of animals. The mean of strength on the grasping test was 133.46±12.08g for the right and 121.74±8.73g for the left anterior paw. There was a difference between the right and left sides. There was no difference between the groups according to sex. There is no statistical difference comparing all functional indexes between sex, independent of the side analyzed. The peroneal functional index showed higher levels than the sciatic and tibial functional index on both sides and sex.ConclusionsThe behavioral and functional assessment of peripheral nerve regeneration are low-cost, easy to perform, and reliable tests. However, they need to be performed by experienced researchers to avoid misinterpretation.

The Correlations Between Walking Analysis Parameters and Q1–Q4 Angles in the Experimental Animal Model of Sciatic Nerve Injury

In the study conducted by Margiana et al., 2015, it has been known that the angle parameters around the point which acts as the meeting point of the lines between the heel and the third fingertip and between finger one and finger five (Q1, Q2, Q3, and Q4) are strongly correlated with Sciatic Functional Index (SFI), Tibial Functional Index (TFI) and Peroneal Functional Index (PFI) in experimental animals with normal walking function, however, whether these parameters can be used in cases of injury is unknown. This study aimed to prove that Q1, Q2, Q3, and Q4 are correlated with SFI, TFI and PFI. This experimental study used 36 Sprague-Dawley rats as the experimental animals that had been approved by the FKUI Ethics Commission. The Seddon 5 classification was done on the rats with end-to-end suture. The rats were allowed to walk in a hallway and different color inks had firstly been given on each rat’s paws. After the formation of foot prints, the measurement of all parameters was made. The Spearman correlation (SPSS 23) analysis showed that there were correlations between SFI, TFI, PFI and Q1, Q2, Q3 and Q4. The correlation coefficient range (r) were categorized as medium correlation. The conclusion of the research that has been conducted is that there are significant correlations between Q1, Q2, Q3, and Q4 with SFI. Thus, Q1, Q2, Q3, and Q4 can be used as one of the predictors of walking function.

Comparison of a collagen membrane versus a fibrin sealant after a peroneal nerve section and repair: a functional and histological study.

To date, fibrin sealant is considered to be one of the most effective substitutes to prevent post-operative fibrosis and to limit neuroma formation after nerve suture. Because fibrin sealant presents a number of drawbacks, more suitable techniques should be considered. The aim of this study was to functionally and histologically compare the efficiency of a fibrin sealant to a resorbable semi-permeable porcine type I collagen membrane after a peroneal nerve lesion and repair on rats. Rats were divided into four groups: (1) a SHAM group (n = 10) in which surgery was performed without damaging the nerve, (2) a LESION group (n = 15) in which the nerve was cut and immediately sutured without additional treatment, (3) a MEMBRANE group (n = 30) in which a collagen membrane was wrapped around the lesion site, and (4) a GLUE group (n = 30) in which the peroneal nerve was coated by fibrin sealant. Peroneal Functional Index (PFI), kinematic analysis of locomotion, muscular atrophy, axonal regrowth, and irritant ranking score (IRS) were performed during three months post-surgery. Our results indicate that at the third month post-surgery, no difference in both the functional recovery and the histological measurement was observed between groups. However, no deleterious effect was observed following the use of the collagen membrane. Indeed, the porcine membrane was well-integrated into the host tissue, with no noticeable foreign body reaction at three months post-surgery. Our preliminary results highlight the fact that the collagen membrane could be used as an alternative to fibrin sealant in peripheral nerve repair surgery. Indeed, animals in which the collagen membrane was used to wrap the lesion site exhibited similar functional and histological results as animals in which a fibrin sealant was used to coat the lesion. The greatest advantage of this membrane is that it could be used as a drug delivery device, regulated by its degradation rate.

Functional recovery after repair of peroneal nerve gap using different collagen conduits

Currently, autologous nerve implantation to bridge a long nerve gap presents the greatest regenerative performance in spite of substantial drawbacks. In this study, we evaluate the effect of two different collagen conduits bridging a peroneal nerve gap. Rats were divided into four groups: (1) the gold standard group, in which a 10-mm-long nerve segment was cut, reversed, and reimplanted between the nerve stumps; (2) the CG-I/III group, in which a type I/III collagen conduit bridged the gap; (3) the CG-I, in which a type I collagen conduit was grafted; and (4) the sham group, in which a surgery was performed without injuring the nerve. Peroneal Functional Index and kinematics analysis of locomotion were performed weekly during the 12 weeks post-surgery. At the end of the protocol, additional electrophysiological tests, muscular weight measurements, axon counting, and g-ratio analysis were carried out. Functional loss followed by incomplete recovery was observed in animals grafted with collagen conduits. At 12 weeks post-surgery, the ventilatory rate of the CG-I group in response to exercise was similar to the sham group, contrary to the CG-I/III group. After KCl injections, an increase in metabosensitive afferent-fiber activity was recorded, but the response stayed incomplete for the collagen groups compared to the sham group. Furthermore, the CG-I group presented a higher number of axons and seemed to induce a greater axonal maturity compared to the CG-I/III group. Our results suggest that the grafting of a type I collagen conduit may present slight better prospects than a type I/III collagen conduit.

Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.

Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form – ergocalciferol versus cholecalciferol – and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair.

Ineficácia da laserterapia aplicada no trajeto do nervo e nas raízes medulares correspondentes

OBJECTIVE: To investigate the influence of low intensity laser irradiation on the regeneration of the fibular nerve of rats after crush injury. METHODS: Twenty-five rats were used, divided into three groups: 1) intact nerve, no treatment; 2) crushed nerve, no treatment; 3) crush injury, laser irradiation applied on the medullary region corresponding to the roots of the sciatic nerve and subsequently on the course of the damaged nerve. Laser irradiation was carried out for 14 consecutive days. RESULTS: Animals were evaluated by functional gait analysis with the peroneal functional index and by histomorphometric analysis using the total number of myelinated nerve fibers and their density, total number of Schwann cells, total number of blood vessels and the occupied area, minimum diameter of the fiber diameter and G-quotient. CONCLUSION: According to the statistical analysis there was no significant difference among groups and the authors conclude that low intensity laser irradiation has little or no influence on nerve regeneration and functional recovery. Laboratory investigation.

Effect of electrical stimulation of the cranial tibial muscle after end-to-side neurorrhaphy of the peroneal nerve in rats

To investigate the efficiency of electrical stimulation in the muscle maintenance and nerve regeneration after end-to-side neurorrhaphy (ESN). Sixty male Wistar rats (Rattus norvegicus) were divided into four experimental groups. Control group (Control), Denervated Group (Denervated); Group with End-to-side neurorrhaphy (ESN); Group with End-to-side neurorrhaphy and electrical stimulation (ESN + ES). We perform electrical stimulation in rats after they had undergone muscle reinnervation by ESN. We collected morphometric and functional data. When comparing the mass of the treated side of cranial tibial muscle (CTM) and that of normal side of CTM, the group ESN + ES (26.12%) exhibited lower mass loss than that of group ESN (37.23%). The peroneal functional index showed that group ESN + ES equaled that of the Control group and showed an evolution of 60.5% while group ESN showed an evolution of 9.5%. In measuring maximum strength of CTM, the group ES + ESN outperformed group ESN. The muscle and nerve morphometry showed superiority of group ES+ESN over ESN group in all parameters. Electrical stimulation is an effective means of maintaining functional muscle and nerve regeneration after end-to-side neurorrhaphy.

Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)

Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.

Functional Recovery Enhancement Following Injury to Rodent Peroneal Nerve by Lion's Mane Mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae)

Peripheral nerve injury represents a huge burden to society. Following peripheral nerve injury, improved behavioral outcome may be the most important evidence of functionality of axonal regeneration after any repair strategy. Nerve-crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruitbodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats with a long-term view toward the possible use of this mushroom in the treatment of nerve injury. Functional recovery was assessed in the behavioral experiment by walking-track analysis and toe-spreading reflex. The peroneal functional index (PFI) was determined before surgery and after surgery, as the rats showed signs of recovery. Analysis of the PFI indicated that the return of hind-limb function occurred by day 10 to 14 and by day 14 to 17 in the treated and control (nontreated) groups, respectively. Normal toe-spreading in the crushed limb was achieved by day 7 to 10 and day 12 to 17 in the treated and control group, respectively. These results suggest that daily administration of aqueous extract of H. erinaceus fresh firuitbodies has a beneficial effect on the recovery of injured rat peroneal nerve in the early stages of regeneration. The PFI and toe-spreading reflex improved faster in the treated group than in the nontreated group.

Functional recovery after peripheral nerve injury and implantation of a collagen guide

Although surgery techniques improved over the years, the clinical results of peripheral nerve repair remain unsatisfactory. In the present study, we compare the results of a collagen nerve guide conduit to the standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves. We assessed behavioral and functional sensori-motor recovery in a rat model of peroneal nerve transection. A 1 cm segment of the peroneal nerve innervating the Tibialis anterior muscle was removed and immediately replaced by a new biodegradable nerve guide fabricated from highly purified type I + III collagens derived from porcine skin. Four groups of animals were included: control animals (C, n = 12), transected animals grafted with either an autologous nerve graft (Gold Standard; GS, n = 12) or a collagen tube filled with an acellular skeletal muscle matrix (Tube-Muscle; TM, n = 12) or an empty collagen tube (Collagen-Tube; CT, n = 12). We observed that 1) the locomotor recovery pattern, analyzed with kinetic parameters and peroneal functional index, was superior in the GS and CT groups; 2) a muscle contraction was obtained in all groups after stimulation of the proximal nerve but the mechanical muscle properties (twitch and tetanus threshold) parameters indicated a fast to slow fiber transition in all operated groups; 3) the muscular atrophy was greater in animals from TM group; 4) the metabosensitive afferent responses to electrically induced fatigue and to two chemical agents (KCl and lactic acid) was altered in GS, CT and TM groups; 5) the empty collagen tube supported motor axonal regeneration. Altogether, these data indicate that motor axonal regeneration and locomotor recovery can be obtained with the insertion of the collagen tube RevolNerv ®. Future studies may include engineered conduits that mimic as closely as possible the internal organization of uninjured nerve.

Promotion of Nerve Regeneration in Peripheral Nerve by Short-Course FK506 after End-to-Side Neurorrhaphy

To discuss the feasibility of peripheral nerve injury treated by end-to-side neurorrhaphy in clinic and to evaluate the effect of short-course FK506 on promoting nerve regeneration after end-to-side neurorrhaphy. Thirty adult male Sprague Dawley rats were randomly divided into 3 groups: Group A, 10 rats received end-to-end anastomosis; Group B, 10 rats received end-to-side neurorrhaphy; Group C, 10 rats received the same operation as Group B. After operation, rats in Groups B and C received muscle injection with saline water (1 mg/kg x d(-1)) and FK506 (1 mg/kg x d(-1)), respectively, both for 4 wk. Histological and morphological examinations were performed 12 wk after the operation. In the 2nd, 4th, 6th, 8th, and 12th wk after operation, function recovery analysis was performed. The results of histological and immunochemistry study (the total number of Schwann cells and the axon numbers at the distal stump of the peroneal nerve, wet weight of extensor digitorum longus muscle) suggested that there were significant differences between Group B (saline water group) and Group C (FK506 group) (P < 0.05), also between Group A (end-to-end group) and Group C (P < 0.05). There were statistically significant differences in function recovery (peroneal functional index and sciatic functional index) between Groups B and C (P < 0.05) and also between Groups A and C (P < 0.05). End-to-side repair combined with FK506 has a potential for application in selected cases of peripheral nerve injury in clinic.

Nerve Bypass Grafting for the Treatment of Neuroma-in-Continuity: An Experimental Study on the Rat

The treatment of neuroma-in-continuity is controversial. To bypass neuroma-in-continuity with a nerve graft using end-to-side neurorrhaphy is considered to be theoretically a good option. To test this therapeutic modality, we performed a nerve bypass graft in a neuroma-in-continuity rat model. An obstructive neuroma-in-continuity was created in a transected peroneal nerve by interposition using the aponeurosis of the spinal muscles. In the experimental animals, (1) immediate, (2) 3-week delayed, or (3) no ulnar nerve bypass graft was performed. The peroneal functional index (PFI), conduction velocity, tibialis anterior muscle weight, and histomorphometric analyses were performed and compared with control (simply cut and repair) animals. On postoperative day 70, the recoveries of the PFI values, conduction velocity, and tibialis anterior muscle weight in the bypassed animals showed no significant differences as compared with the control animals, and the extent of these recoveries in the bypassed animals were significantly superior to those in the no-graft animals. In the histomorphometric analysis, the mean percent nerve in the bypassed animals was significantly larger than that in the no-graft animals. In conclusion, this technique may be a good alternative to the current therapeutic techniques for neuroma-in-continuity when there is a significant retained function.

The Rho-Associated Kinase Inhibitor Fasudil Hydrochloride Enhances Neural Regeneration after Axotomy in the Peripheral Nervous System

The Rho family of small GTPases is responsible for various processes involving actin cytoskeleton in eukaryotic cells, including neurite outgrowth. Several substances found at the peripheral nerve injury site were shown to activate one member of this family, Rho. The activation of Rho leads to neurite outgrowth inhibition and the development of posttraumatic neuropathic pain. The authors used the clinically tested Rho-associated kinase inhibitor fasudil hydrochloride to enhance the functional recovery of the peripheral nerve in the rat. In the peroneal nerve interpositional graft model, the authors administered fasudil (experimental groups) or saline (control groups) (1) intraperitoneally and (2) directly into the graft by microinjection (n = 6 animals per experimental condition). Neural recovery was assessed during postoperative follow-up lasting 80 days by peroneal functional index, electrophysiologic, and histomorphometric analyses. The peroneal functional index returned to values not significantly different from preoperative values on days 55 (fasudil injected into the graft) and 60 (fasudil injected intraperitoneally) in the experimental groups. In the control groups, this took 70 (saline injected intraperitoneally) and 75 days (saline injected into the graft). These results are supported by electrophysiologic and histomorphologic assessments. The authors determined that fasudil hydrochloride was capable of accelerating the functional regeneration after peripheral nerve axotomy, which is consistent with the results of reports about Rho cascade disruption in the central nervous system. Because fasudil hydrochloride is a clinically tested drug, it could be used to enhance neural regeneration in human patients as well.

End-to-Side Nerve Coaptation

The aim of this experimental study was to evaluate the effects of end-to-side coaptation of the proximal end of a severed nerve to the same intact nerve, in addition to traditional end-to-side coaptation of the distal end, with an aim to use the intact nerve as a nerve conduit in a rat model and to compare the functional and histologic results of this modality to those obtained after nerve grafting and traditional end-to-side nerve coaptation. In group A, a peroneal nerve defect measuring 1 cm was created in the left hind limb, and a nerve graft 1 cm long was used to bridge the defect. In group B, only the distal stump of the peroneal nerve was coapted to the intact tibial nerve. In group C, both ends of the peroneal nerve defect were coapted to the intact tibial nerve in an end-to-side fashion 1.5 cm apart from each other, and in group D, the peroneal nerve defect was left unrepaired. Group E was consisted of nonoperated peroneal nerves that were used to obtain normative data. Although significantly higher myelinated axon densities were observed in groups B and C compared with group A and group E, total number of the myelinated axons was significantly higher only in group C. Peroneal functional index assessments demonstrated that nerve recovery in the peroneal nerve was similar in groups A and C, and both were better than those observed in groups B and D. Collectively, these results suggest that end-to-side coaptation of both ends of a severed nerve to an intact nerve, in case of a nerve defect in this length, may serve as an alternative for nerve grafting.

Motor Functional and Morphological Findings following End-To-Side Neurorrhaphy in the Rat Model

Nerve repair cannot always be achieved by the conventional end-to-end technique. This study evaluated the functional recovery of nerves repaired with end-to-side neurorrhaphy in a rat model. The right peroneal nerves of 80 female rats were transected and divided into four groups. In group A, the nerve ends were separated and remained unrepaired; in group B, the distal peroneal ends were directly sutured to the epineurium of the tibial nerves in end-to-side fashion; in group C, the distal ends were sutured through an epineurial window at the repair site in end-to-side fashion; and in group D, the nerve ends were reconnected by the traditional end-to-end technique. Evaluation included gait analysis by calculation of a peroneal functional index, measurement of contractile function of the extensor digitorum longus muscle, wet weight of the extensor digitorum longus, and histological examination. The findings of this study suggested the following: (a) end-to-side neurorrhaphy allows effective motor functional recovery, demonstrated by earlier improvement of the peroneal functional index, stronger muscle contractile function, greater muscle weight, and higher density of regenerated axons compared with unrepaired nerves; (b) removal of the epineurium of the donor nerve at the nerve coaptation site increases the effectiveness of end-to-side neurorrhaphy, but the epineurium appears to be a partial barrier to axonal regeneration; (c) removal of the epineurium does not affect the structure and function of the donor nerve; and (d) end-to-end repair achieved the best functional recovery among the four groups; therefore, end-to-side repair should be considered as a potential alternative only when no proximal nerve is available.

Functional indices for sciatic, peroneal, and posterior tibial nerve lesions in the mouse

The sciatic functional index previously described in rats has proven to be a reliable index of functional recovery following sciatic nerve injury and repair. A similar functional assay of sciatic, peroneal, and posterior tibial nerve lesions was developed in a mouse model. Forty-eight C57/BL6 mice were randomly divided into 4 groups: sham surgery, sciatic nerve transection, peroneal nerve transection, and posterior tibial nerve transection. Preoperative and postoperative (48 hours) walking tracks were obtained. The pawprints were analyzed in a blinded fashion for measurements of print length (PL), toe spread (TS), intermediate toe spread (IT), and the orthogonal distance from the toe of one paw to the hind pad of the opposite paw (TOF). Multiple linear regression analysis was performed using these measurements to determine their significance and appropriate weighted contribution to the index formula for each nerve lesion. For the sciatic functional index, changes in the PL (P = 0.0092) and TS (P = 0.0008) were significant, resulting in an R2 value of 0.88. For the peroneal functional index, only TS (P < 0.0001) was significant with R2 = 0.83. For the posterior tibial index, only PL (P < 0.0001) was significant with R2 = 0.89. Formulas for a sciatic, peroneal, and posterior tibial functional index were created based on the coefficients derived from the multiple linear regression analysis. The indices that were developed will allow investigators to assess functional recovery following specific nerve lesions in mice. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:119-124 1998

Sex Hormones Affect Muscle Contractility and Motor Functional Recovery Following Peroneal Nerve Crush

This study was performed to investigate possible sex differences in the contractile responses of the reinnervated extensor digitorum longus (EDL) muscle. Electromechanical studies on muscle stimulated indirectly through its nerve provided information on muscle contractility during early reinnervation. Locomotor functional recovery was followed by analyzing changes in footprint parameters over time. At 9 days postsurgery, nerve crush affected negatively many isometric contractile parameters, including twitch peak rate and contraction amplitude, as well as tetanic peak rate, contraction amplitude, and half relaxation time (HRT), regardless of sex. Female EDLs had a greater tetanic peak contraction amplitude and fully recovered twitch HRT levels. While this sex difference is clearly apparent in muscle contractility, it was abolished when considering motor functional recovery. Locomotor tests were less sensitive in demonstrating sex differences during recovery from nerve crush. Peroneal functional index (PFI), a parameter well-described by Bain in 1989, is a paradigm which compares all footprint changes incurred in a rat after peroneal nerve crush, using data obtained from uncrushed side to normalize values. PFI indicated that removal of the sex steroids seriously hindered recovery of motor function regardless of gender.

Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat.

Quantification of peripheral nerve regeneration in animal studies of nerve injury and repair by histologic, morphologic, and electrophysiologic parameters has been controversial because such studies may not necessarily correlate with actual nerve function. This study modifies the previously described sciatic functional index (SFI), tibial functional index (TFI), and peroneal functional index (PFI) based on multiple linear regression analysis of factors derived from measurements of walking tracks in rats with defined nerve injuries. The factors that contributed to these formulas were print-length factor (PLF), toe-spread factor (TSF), and intermediary toe-spread factor (ITF). It was shown that animals with selective nerve injuries gave walking tracks that were consistent, predictable, and based on known neuromuscular deficits. The new formula for sciatic functional index was compared with previously described indices. The sciatic functional index, tibial functional index, and peroneal functional index offer the peripheral nerve investigator a noninvasive quantitative assessment of hindlimb motor function in the rat with selective hindlimb nerve injury.