Prosaposin in the rat oviductal epithelial cells.

Prosaposin (PSAP) has two forms: a precursor and a secreted form. The secreted form has neurotrophic, myelinotrophic, and myotrophic properties. The precursor form is a precursor protein of saposins A-D. Although the distribution of PSAP in male reproductive organs is well known, its distribution in female reproductive organs, especially in the oviduct, is unclear. Immunoblots and immunohistochemistry of oviducts showed that oviductal tissues contain PSAP proteins, and a significant increase in PSAP was observed in the estrus-metestrus phase compared to the diestrus-proestrus phase in the ampulla. To identify PSAP trafficking in cells, double-immunostaining was performed with antibodies against PSAP in combination with sortilin, mannose 6 phosphate receptor (M6PR), or low-density lipoprotein receptor-related protein 1 (LRP1). PSAP and sortilin double-positive reactions were observed near the nuclei, as well as in the apical portion of microvillous epithelial cells, whereas these reactions were only observed near the nuclei of ciliated epithelial cells. PSAP and M6PR double-positive reactions were observed near the nuclei of microvillous and ciliated epithelial cells. PSAP and M6PR double-positive reactions were also observed in the apical portion of microvillous epithelial cells. PSAP and LRP1 double-positive reactions were observed in the plasma membrane and apical portion of both microvillous and ciliated epithelial cells. Immunoelectron staining revealed PSAP immunoreactive small vesicles with exocytotic features at the apical portion of microvillous epithelial cells. These findings suggest that PSAP is present in the oviductal epithelium and has a pivotal role during pregnancy in providing an optimal environment for gametes and/or sperm in the ampulla.

Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: a case report and literature review.

BACKGROUND: The most common sites of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been reported to be the liver, lung, bone, and adrenal glands, but there have also been many reports of cases of multiple recurrence. The prognosis after recurrence is poor, with reported median survival after recurrence of HCC ranging from 9 to 19 months. Here, we report a case of long-term survival after recurrence of pharyngeal metastasis following living-donor liver transplantation (LDLT) for HCC within the Milan criteria, by resection of the metastatic region and cervical lymph node dissection. CASE PRESENTATION: A 47-year-old man with a Model End-stage Liver Disease (MELD) score of 11 underwent LDLT for HCC within the Milan criteria for liver cirrhosis associated with hepatitis B virus infection, with his 48-year-old elder brother as the living donor. One year and 10 months after liver transplantation, he visited a nearby hospital with a chief complaint of discomfort on swallowing. A pedunculated polyp was found in the hypopharynx, and biopsy revealed HCC metastasis. We performed pharyngeal polypectomy. Two years later, cervical lymph node metastasis appeared, and neck lymph node dissection was performed. Although recurrence subsequently occurred three times in the grafted liver, the patient is still alive 12 years and 10 months after recurrence of pharyngeal metastasis. He is now a tumor-free outpatient taking sorafenib. CONCLUSION: It is necessary to recognize that the nasopharyngeal region is a potential site of HCC metastasis. Prognostic improvement can be expected with close follow-up, early detection, and multidisciplinary treatment, including radical resection.

[A retrospective study on parotid carcinoma].

We retrospectively analyzed the clinicopathological factors affecting survival in patients with previously untreated parotid carcinoma. The subjects were 50 patients treated in our department from 1987 through 2011. The T stage was T1, T2, T3, and T4 in 4 patients, 11 patients, 9 patients, and 26 patients, respectively. The N stage was N0, N1, and N2 in 36 patients, 3 patients, and 11 patients, respectively. The clinical stage was I, II, III, and IV in 4 patients, 10 patients, 7 patients, and 29 patients, respectively. Histopathologically, eleven tumor types were observed; mucoepidermoid carcinoma was the most common. The overall 5-year survival rate was 72.1%, and the disease-specific 5-year survival rate was 74.0% in 42 patients who received radical surgery. Twelve patients relapsed; the site of relapse was the primary site alone in 2, in the neck alone in 3 patients, in the neck with distant metastases in 2 patients, and in distant metastatic site (s) alone in 5 patients. Univariate analysis showed that significant prognostic factors for overall survival rates were the T stage, cervical lymph node metastasis, clinical stage, grade, facial nerve palsy, and tumor size. We concluded that patients at high risk of recurrence should receive adjuvant therapy to improve the therapeutic outcomes.

Distribution of prosaposin in rat lymphatic tissues.

Prosaposin (PSAP) is as a trophic factor and an activator protein for sphingolipid hydrolase in lysosomes. We generated a specific antibody to PSAP and examined the spatiotemporal distribution of PSAP-immunoreactive (PSAP-IR) cells in the lymphatic tissues of Wistar rats. Immunoblots of tissue homogenates separated electrophoretically showed a single band for PSAP in brain but two bands in spleen. PSAP-IR cells were distributed in both the red and white pulp of the spleen, in both the cortex and medulla of the thymus and in mesenteric lymph nodes. Many PSAP-IR cells were found in the dome portion of Peyer's patches and the number of PSAP-IR cells increased with the age of the rat. To identify the PSAP-IR cells, double- and triple-immunostainings were performed with antibodies against PSAP, CD68 and CD1d. The large number of double- and triple-positive cells suggested that antigen-presenting cells contained much PSAP in these lymphatic tissues. Intense expression of PSAP mRNA, examined by in situ hybridisation, was observed in the red pulp and corona of the spleen. In rats, the PSAP gene generates two alternative splicing forms of mRNA: Pro+9 containing a 9-base insertion and Pro+0 without the insertion. We examined the expression patterns of the alternative splicing forms of PSAP mRNA in the spleen. The presence of both types of mRNA (Pro+9 and Pro+0) indicated that the spleen contains various types of prosaposin-producing and/or secreting cells. These findings suggest diverse functions for PSAP in the immune system.

Tracking of Prosaposin, a Saposin Precursor, in Rat Testis.

We tracked prosaposin (PSAP), a trophic factor, using an antibody specific to its proteolytic portion and an antibody to sortilin that traffics PSAP only to the lysosome. Immunostaining revealed that PSAP was distributed mainly on the basal side of seminiferous tubules, where many Sertoli cells and pachytene spermatocytes contained PSAP and its distribution differed depending on the stage of the spermatogenic cycle. The PSAP-sortilin complex was sorted to large lysosomes in the basal cytoplasm of Sertoli cells, where it may be processed into saposins. In contrast, in the thinner apical cytoplasm of Sertoli cells, PSAP in small lysosomes was transported to the apical side around sperm heads or into the lumen for secretion. The results of in situ hybridization analyses suggested that immature tubular cells in young animals produce PSAP to self-stimulate proliferation. However, in adults, not only Sertoli cells but also pachytene spermatocytes produce and secrete PSAP around germ cells or into the tubular lumen to stimulate cell proliferation or differentiation in a paracrine or autocrine manner. In summary, PSAP is not only a precursor of lysosomal enzymes but also a pivotal trophic factor in organogenesis in the immature testis and spermatogenesis in the mature testis.

Comparison of the Signal Intensity of Vestibular Schwannoma Between Growing and Nongrowing Tumors.

OBJECTIVES/HYPOTHESIS: To determine the relationship between signal intensity on gadolinium (Gd)-enhanced magnetic resonance images and growth of vestibular schwannomas (VSs). STUDY DESIGN: Cross-sectional study. METHODS: In this cross-sectional study, we retrospectively reviewed the data of 31 patients with VSs who underwent magnetic resonance imaging (MRI). The mean signal intensities within the regions of interest in the tumor, pons, and temporal muscles were measured on Gd-enhanced T1-weighted MRI. Relative intensity ratios were calculated as follows: T/N pons ratio (T/Np) is the tumor signal intensity/pons signal intensity and T/N muscle ratio (T/Nm) is the tumor signal intensity/temporal muscle signal intensity. Volume measurements were used to assess the tumor size. Growth rate was determined by assessing previous imaging studies. Growing VS was defined as a tumor with a growth rate >100 mm3 /year. RESULTS: The mean (standard deviation) T/Np and T/Nm were 1.47 (0.27) and 1.50 (0.24), respectively, in nongrowing tumors and 1.78 (0.17) and 1.90 (0.12), respectively, in growing tumors. The T/Np and T/Nm differed significantly between the two groups (T/Np, P < .001; T/Nm, P < .001). Receiver operating characteristic curve analysis showed that cutoffs of 1.56 and 1.76 for T/Np (93.33% sensitivity, 75.00% specificity) and T/Nm (100.00% sensitivity, 93.75% specificity), respectively, could be used to diagnose a growth rate of >100 mm3 /year. The area under the curve was 0.85 (95% confidence interval, 0.70-1.00) for T/Np and 0.94 (0.82-1.00) for T/Nm. CONCLUSION: Growing VSs show higher signal intensities on Gd-enhanced MRI. Thus, measuring the signal intensity of VS on Gd-enhanced MRI may aid in predicting VS growth. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:198-203, 2022.

Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity.

We investigated the effects of Rho-associated kinase (ROCK) on migration and cytoskeletal organization in primary human osteoblasts and Saos-2 human osteosarcoma cells. Both cell types were exposed to two different ROCK inhibitors, Y-27632 and HA-1077. In the improved motility assay used in the present study, Y-27632 and HA-1077 significantly increased the migration of both osteoblasts and osteosarcoma cells on plastic in a dose-dependent and reversible manner. Fluorescent images showed that cells of both types cultured with Y-27632 or HA-1077 exhibited a stellate appearance, with poor assembly of stress fibers and focal contacts. Western blotting showed that ROCK inhibitors reduced myosin light chain (MLC) phosphorylation within 5 min without affecting overall myosin light-chain protein levels. Inhibition of ROCK activity is thought to enhance the migration of human osteoblasts through reorganization of the actin cytoskeleton and regulation of myosin activity. ROCK inhibitors may be potentially useful as anabolic agents to enhance the biocompatibility of bone and joint prostheses.

Intratympanic Insulin-like Growth Factor-1 Administration Via the Otic Bulla in a Severe Facial Paralysis Model.

HYPOTHESIS: We investigated the treatment effect of intratympanic insulin-like growth factor-1 (IGF-1) on severe facial paralysis in guinea pigs. BACKGROUND: The use of regenerative medicine involving growth factors has been reported in the treatment of peripheral nerve diseases. IGF-1 plays a crucial role in nerve regeneration. METHODS: We performed the following procedures on guinea pigs. In the normal group (n = 7), no procedure was performed. In the saline (n = 7) and IGF-1 (n = 7) groups, facial paralysis was induced by freezing of the facial canal. Subsequently, in the saline and IGF-1 groups, a gelatin hydrogel impregnated with 100 µL saline and 400 µg/100 µL IGF-1, respectively, was placed in the facial canal. Facial nerve functions were evaluated using three test batteries: facial movement observation, electrophysiological testing, and histological assessment. RESULTS: At 10 weeks postoperatively, the facial movement scores for the IGF-1 group were improved compared to those in the saline group. The conductive velocity was significantly faster in the IGF-1 group than in the saline group. There was a significant between-group difference in the nerve fiber number and myelin thickness. CONCLUSION: Intratympanic IGF-1 administration improved facial nerve regeneration. This novel method could provide prompt ambulatory regenerative treatment and reduce the incidence of poor recovery in patients with severe facial paralysis.

The expression of prosaposin and its receptors, GRP37 and GPR37L1, are increased in the developing dorsal root ganglion.

Prosaposin (PSAP), a highly conserved glycoprotein, is a precursor of saposins A-D. Accumulating evidence suggests that PSAP is a neurotrophic factor, as well as a regulator of lysosomal enzymes. Recently, the orphan G-protein-coupled receptors GPR37 and GPR37L1 were recognized as PSAP receptors, but their functions have not yet been clarified. In this study, we examined the distribution of PSAP and its receptors in the dorsal root ganglion (DRG) during development using specific antibodies, and showed that PSAP accumulates primarily in lysosomes and is dispersed throughout the cytoplasm of satellite cells. Later, PSAP colocalized with two receptors in satellite cells, and formed a characteristic ring shape approximately 8 weeks after birth, during a period of rapid DRG development. This ring shape, which was only observed around larger neurons, is evidence that several satellite cells are synchronously activated. We found that sortilin, a transporter of a wide variety of intracellular proteins containing PSAP, is strongly localized to the inner side of satellite cells, which contact the neuronal surface. These findings suggest that PSAP and GPR37/GPR37L1 play a role in activating both satellite and nerve cells.

Verbalization, Categorization, and Evaluation of Fundamental Surgical Skills: An Expert Consensus in Open Head and Neck Surgery.

Objective: This study aimed to verbalize fundamental surgical skills required for open head and neck surgery (OHNS), to organize them by categorization, and to establish a consensus among surgeons regarding the importance and difficulty of each skill. Summary Background Data: Improvement of fundamental surgical skills is the core of surgical education; however, surgical skills are not yet organized, and consensus in any surgical field remains uncertain. Methods: Fundamental surgical skills during OHNS were collected from surgical textbooks, real surgeries, and expert interviews. The items were analyzed to calculate the frequency of words and were categorized by 2 expert surgeons. After consensus on the importance and difficulty of each item was established by 15 expert surgeons using a Delphi survey, principal component (PC) analysis was performed to integrate importance and difficulty into a single parameter. Results: Sixty skills were verbalized and categorized into 7 categories: "skin flap elevation (n = 6)," "vessel management (n = 9)," "nerve preservation (n = 8)," "instrument handling (n = 11)," "counter traction (n = 7)," "tissue exposure (n = 9)," and "flow and planning (n = 10)." In the Delphi survey, expert consensus was established after 2 voting rounds (Cronbach's α ≥ 0.80). The "counter traction" and "flow and planning" categories had high PC scores, which indicate priority in surgical education. Conclusion: Fundamental OHNS skills were verbalized, categorized, and evaluated via expert consensus. Assessment of surgeons' skills by the structured items hereby developed will help standardize the quality of OHNS and improve patient outcomes.

Prosaposin and its receptors GRP37 and GPR37L1 show increased immunoreactivity in the facial nucleus following facial nerve transection.

Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and PS are widely contained in various tissues. The brain, skeletal muscle, and heart cells predominantly contain unprocessed PS rather than saposins. PS and PS-derived peptides stimulate neuritogenesis and increase choline acetyltransferase activity in neuroblastoma cells and prevent programmed cell death in neurons. We previously detected increases in PS immunoactivity and its mRNA in the rat facial nucleus following facial nerve transection. PS mRNA expression increased not only in facial motoneurons, but also in microglia during facial nerve regeneration. In the present study, we examined the changes in immunoreactivity of the PS receptors GPR37 and GPR37L1 in the rat facial nucleus following facial nerve transection. Following facial nerve transection, many small Iba1- and glial fibrillary acidic protein (GFAP)-positive cells with strong GPR37L1 immunoreactivity, including microglia and astrocytes, were observed predominately on the operated side. These results indicate that GPR37 mainly works in neurons, whereas GPR37L1 is predominant in microglia or astrocytes, and suggest that increased PS in damaged neurons stimulates microglia or astrocytes via PS receptor GPR37L1 to produce neurotrophic factors for neuronal recovery.

[The effects of a novel local ventilation system to reduce the health hazard to students during gross anatomy courses].

Formaldehyde or formalin is indispensable not only as a preservative but also as a disinfectant of cadavers for gross anatomy. It has recently attracted a great deal of attention as a health hazard for students and lecturers. To reduce the concentration of formaldehyde gas (FAG), we improved a novel local ventilation system of the push-pull type. This is the first report dealing with the effects of this ventilation system on the health of students before (over 1 ppm) and after (0.1 ppm) the installation. The percentages of students with lacrymal symptoms or airway irritation were reduced to a third of what they were before the installation. In particular, the number of those with continuously strong symptoms was reduced to a sixth of the pre-installation levels. This local ventilation system draws in fresh air from outside, and directs it to the breathing zone of the students, effectively reducing their symptoms.

Phylogenetic investigation of Dogiel's pericellular nests and Cajal's initial glomeruli in the dorsal root ganglion.

Cajal's initial glomeruli (IG) and Dogiel's pericellular nests (PCNs) were first described from methylene blue preparations of healthy animal tissues around the beginning of the last century. Since that time, although many reports have been published concerning these structures, few have focused on their development and phylogeny in healthy animals. The aim of this study was to examine the phylogenetic development of the sensory neurons in Cajal's IG (also called axonal glomeruli) and Dogiel's PCNs in the dorsal root ganglion (DRG) of the healthy adult frog, chick, rat, and rabbit. The three-dimensional architecture of the neurons was observed in ganglia by scanning electron microscopy after removal of the connective tissue. The neurons in the DRG of fish are known to be bipolar, but DRG neurons in the species examined here were found to be pseudounipolar, with single stem processes. The proportion of neurons having IG or PCNs increased with increasing phylogenetic complexity in the species examined here. Cajal's initial glomeruli, the convolution of the stem process near the parent cell body: In frogs, the ganglia were small and the neuronal stem processes were very short and straight. In chicks, the stem processes were longer; sometimes very long, tortuous processes were observed. However, no neurons with typical IG were observed in either species. Typical IG were observed in rats and rabbits; their occurrence was much more frequent in rabbits. Pseudounipolarization, i.e., the transition from bipolar to pseudounipolar neurons, is thought to save space, limit the length of neuronal processes, and reduce conduction time. However, an explanation of the evolutionary advantage of the IG, which is formed by the excessive prolongation of the stem process, remains elusive. The cytological and electrophysiological importance of IG has been discussed. Dogiel's pericellular nests (PCNs), which resemble balls of yarn made of thin unmyelinated nerve fibers around DRG neurons, have been observed in the DRG of rats and rabbits, but not in frogs or chicks. This interesting structure shows not only ontogenetic development in healthy animals but also phylogenetic development among species. The nerve fibers in the PCNs were less than 1.2 mum in diameter and had some varicosities. An immunohistochemical study using anti-tyrosine hydroxylase (TH) antibody revealed that some PCNs contain TH-positive nerve fibers and varicosities. Such TH-positive PCNs disappear after sympathectomy. These results suggest that the PCNs are made up of autonomic nerve fibers.

Changes in expression of prosaposin in the rat facial nerve nucleus after facial nerve transection.

Prosaposin is the precursor of saposins A, B, C and D, which are activators of sphingolipid hydrolases. In addition, unprocessed prosaposin functions as a neurotrophic factor in the central and peripheral nervous systems by acting to prevent neuronal apoptosis, to elongate neurites and to facilitate myelination. In this study, the expression pattern of prosaposin in the facial nerve nucleus after facial nerve transection was examined by immunohistochemistry and in situ hybridization. Prosaposin immunoreactivity in the neurons on the operated side facial nerve nucleus showed a biphasic pattern: it was significantly increased on day 3 after transection, decreased dramatically on day 7, started to increase gradually on day 14 and reached another peak on day 21 after transection. Significant increases in the levels of prosaposin mRNA were identified in the neurons on the operated side, suggesting that prosaposin was synthesized vigorously by the neurons themselves in the case of facial nerve transection. The diverse changes in prosaposin immunoreactivity during the process of facial nerve regeneration may reflect the diverse neurotrophic activities of prosaposin in facial motoneurons.

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1.

CONCLUSION: Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4 + T cells play a more important role in host defense against virus replication. OBJECTIVE: To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. MATERIAL AND METHODS: Eight weeks after recovery from primary facial paralysis caused by inoculating the auricle with HSV-1 the auricle was scratched and mice (n = 69) were given an i.p. injection of either anti-CD4 (n = 46) or anti-CD8 (n = 23) monoclonal antibody to deplete specific T-lymphocyte subsets. Following this reactivation procedure, the rate of recurrent facial paralysis was compared between the two models. The GG were examined histopathologically and using polymerase chain reaction to detect HSV-1 DNA. RESULTS: Facial paralysis developed in 42% of mice in the anti-CD4 model and in 13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both models. Histopathologically, neurons were destroyed in parts of the GG and numerous virus particles were seen in the surviving neurons.

A prosaposin-derived Peptide alleviates kainic Acid-induced brain injury.

Four sphingolipid activator proteins (i.e., saposins A-D) are synthesized from a single precursor protein, prosaposin (PS), which exerts exogenous neurotrophic effects in vivo and in vitro. Kainic acid (KA) injection in rodents is a good model in which to study neurotrophic factor elevation; PS and its mRNA are increased in neurons and the choroid plexus in this animal model. An 18-mer peptide (LSELIINNATEELLIKGL; PS18) derived from the PS neurotrophic region prevents neuronal damage after ischemia, and PS18 is a potent candidate molecule for use in alleviating ischemia-induced learning disabilities and neuronal loss. KA is a glutamate analog that stimulates excitatory neurotransmitter release and induces ischemia-like neuronal degeneration; it has been used to define mechanisms involved in neurodegeneration and neuroprotection. In the present study, we demonstrate that a subcutaneous injection of 0.2 and 2.0 mg/kg PS18 significantly improved behavioral deficits of Wistar rats (n = 6 per group), and enhanced the survival of hippocampal and cortical neurons against neurotoxicity induced by 12 mg/kg KA compared with control animals. PS18 significantly protected hippocampal synapses against KA-induced destruction. To evaluate the extent of PS18- and KA-induced effects in these hippocampal regions, we performed histological evaluations using semithin sections stained with toluidine blue, as well as ordinal sections stained with hematoxylin and eosin. We revealed a distinctive feature of KA-induced brain injury, which reportedly mimics ischemia, but affects a much wider area than ischemia-induced injury: KA induced neuronal degeneration not only in the CA1 region, where neurons degenerate following ischemia, but also in the CA2, CA3, and CA4 hippocampal regions.

Lectin histochemical study on the olfactory organ of the newt, Cynops pyrrhogaster, revealed heterogeneous mucous environments in a single nasal cavity.

Expression patterns of glycoconjugates were examined by lectin histochemistry in the nasal cavity of the Japanese red-bellied newt, Cynops pyrrhogaster. Its nasal cavity consisted of two components, a flattened chamber, which was the main nasal chamber (MNC), and a lateral diverticulum called the lateral nasal sinus (LNS), which communicated medially with the MNC. The MNC was lined with the olfactory epithelium (OE), while the diverticulum constituting the LNS was lined with the vomeronasal epithelium (VNE). Nasal glands were observed beneath the OE but not beneath the VNE. In addition, a secretory epithelium was revealed on the dorsal boundary between the MNC and the LNS, which we refer to as the boundary secretory epithelium (BSE) in this study. The BSE seemed to play an important role in the construction of the mucous composition of the VNE. Among 21 lectins used in this study, DBA, SBA and Jacalin showed different staining patterns between the OE and the VNE. DBA staining showed remarkable differences between the OE and the VNE; there was intense staining in the free border and the supporting cells of the VNE, whereas there was no staining or weak staining in the cells of the OE. SBA and Jacalin showed different stainings in the receptor neurons for the OE and the VNE. Furthermore, UEA-I and Con A showed different stainings for the nasal glands. UEA-I showed intense staining in the BSE and in the nasal glands located in the ventral wall of the MNC (VNG), whereas Con A showed intense staining in the BSE and in the nasal glands located in the dorsal and medial wall of the MNC (DMNG). The DMNG were observed to send their excretory ducts into the OE, whereas no excretory ducts were observed from the VNG to the OE or the VNE. These results suggested that the secretion by the supporting cells as well as the BSE and the DMNG establishes that there are heterogeneous mucous environments in the OE and the VNE, although both epithelia are situated in the same nasal cavity.

Efficacy of early treatment of Bell's palsy with oral acyclovir and prednisolone.

OBJECTIVE: To investigate the therapeutic effects of acyclovir and prednisolone in relation to the timing of treatment in Bell's palsy. STUDY DESIGN: This was a retrospective study of 480 Bell's palsy patients who were treated with oral acyclovir and prednisolone (94 cases) or prednisolone alone (386 cases). PATIENTS: Patients met the after criteria: (1) severe or complete Bell's palsy with a score lower than 20 on the 40-point Yanagihara facial score and (2) treatment started within 7 days after onset. The patients were treated with oral prednisolone (60-40 mg/day) with or without oral acyclovir (2,000 mg/day). MAIN OUTCOME MEASURE: Rate of recovery, which was defined as a facial score of 36 or more, and the absence of contracture with synkinesis. RESULTS: The overall recovery rate of patients treated with acyclovir and prednisolone was 95.7 percent, which was better than that of patients treated with prednisolone alone (88.6%). The recovery rate in patients who began the combined therapy within 3 days of the onset of palsy was 100 percent and early treatment resulted in early remission. In contrast, the recovery rate in patients who started the combined therapy more than 4 days after onset was 86.2 percent. CONCLUSION: These results suggest that early diagnosis and treatment within 3 days of the onset of paralysis are necessary for maximal efficacy of combined acyclovir and prednisolone therapy for Bell's palsy.

Pathophysiology of facial nerve paralysis induced by herpes simplex virus type 1 infection.

Herpes simplex virus type 1 (HSV-1) has been proven to be a cause of Bell's palsy; however, the underlying pathophysiology of the facial nerve paralysis is not fully understood. We established a mouse model with facial nerve paralysis induced by HSV-1 infection simulating Bell's palsy and investigated the pathophysiology of the facial nerve paralysis. The time course of the R1 latency in the blink reflex tests paralleled the recovery of the facial nerve paralysis well, whereas electroneurographic recovery tended to be delayed, compared to that of the paralysis; these responses are usually seen in Bell's palsy. On histopathologic analysis, intact, demyelinated, and degenerated nerves were intermingled in the facial nerve in the model. The similarity of the time course of facial nerve paralysis and the electrophysiological results in Bell's palsy and the model strongly suggest that the pathophysiological basis of Bell's palsy is a mixed lesion of various nerve injuries.

Effects of acyclovir on facial nerve paralysis induced by herpes simplex virus type 1 in mice.

OBJECTIVES: Bell's palsy has recently been claimed to be caused by herpes simplex virus type 1 (HSV-1) infection. The anti-viral agent acyclovir is a specific inhibitor of herpesvirus replication, and the most effective agent for the treatment herpesvirus infection. The purpose of this experiment was to assess the effect of acyclovir on the facial nerve paralysis included by HSV-1 infection. METHODS: We succeeded in producing an animal model of acute and transient facial nerve paralysis induced with HSV-1 neuritis simulating human Bell's palsy. In this study, acyclovir administration was performed before and after facial nerve paralysis, and continued for 5 days. Controls were given phosphate-buffer saline (PBS) instead of acyclovir, and the incidence and duration of facial nerve paralysis was compared in the acyclovir groups and controls. RESULTS: The incidence of facial nerve paralysis was significantly lower in the group given acyclovir before the paralysis than in the controls, and the duration of facial nerve paralysis was shorter. CONCLUSIONS: Administration of acyclovir before the paralysis reduced the incidence and duration of facial nerve paralysis. Administration of acyclovir after the paralysis improved the duration of facial nerve paralysis.