Bilateral Pallidal Stimulation with Directional Leads for Primary Focal Lingual Dystonia.

There have been limited studies regarding stereotactic and functional neurosurgery for lingual dystonia. Here, we report a patient with primary lingual dystonia who showed significant improvement after bilateral deep brain stimulation (DBS). A 42-year-old woman presented with a 5- to 6-year history of tongue protrusion; however, she lacked a significant medical or medication history before onset. She presented with gradually worsening symptoms and was diagnosed with idiopathic lingual dystonia. Her tongue was injected with botulinum toxin on 6 occasions; however, it had a limited effect. Oral medications were ineffective. She underwent DBS since her involuntary tongue movements were causing nocturnal breathing problems. Directional leads were bilaterally inserted into the internal segment of the globus pallidus (GPi). The directional part of each lead was inserted at the GPi bottom on both sides. The posteromedial contacts were used to deliver stimulation. After 1.5 years, the patient's Burke-Fahn-Marsden dystonia rating scale score improved from 9 to 1.5 and 2 to 1 for movement and disability, respectively. This case demonstrated the effectiveness of bilateral GPi-DBS. Placing the directional part of the lead in the GPi bottom could improve the stimulation effects.

The Behavior and Acrosomal Status of Mouse Spermatozoa In Vitro, and Within the Oviduct During Fertilization after Natural Mating.

Although 90%-100% of mouse oocytes can be fertilized in vitro with capacitated spermatozoa within 1 h after insemination, oocytes within the oviduct are fertilized one by one over a period of several hours. In vitro experiments showed that both acrosome-intact and acrosome-reacted spermatozoa entered the cumulus oophorus, but that acrosome-reacted spermatozoa reached the surface of oocytes more readily than acrosome-intact spermatozoa. During the period of fertilization within the oviduct, acrosome-reacted spermatozoa were seen throughout the isthmus, but with higher incidence in the upper than in the mid- and lower segments of the isthmus. Very few spermatozoa were present in the ampulla, and almost all were acrosome reacted. Although the cumulus oophorus and zona pellucida are known to be able to induce or facilitate the acrosome reaction of spermatozoa, this picture makes it likely that almost all fertilizing mouse spermatozoa within the oviduct begin to react before ascending from the isthmus to the ampulla. We witnessed a reacted spermatozoon that stayed on the zona pellucida of a fertilized oocyte for a while; it then moved out of the cumulus before reaching the zona pellucida of the nearby unfertilized oocyte. We noted that only a few spermatozoa migrate from the isthmus to the ampulla during the progression of fertilization, and this must be one of the reasons why we do not see many spermatozoa swarming around a single oocyte during in vivo fertilization.

Behavior of Mouse Spermatozoa in the Female Reproductive Tract from Soon after Mating to the Beginning of Fertilization.

Using transgenic mice with spermatozoa expressing enhanced green fluorescent protein in their acrosome and red fluorescent protein in their midpiece mitochondria, we followed the behavior of spermatozoa within the female genital tract after natural mating. When examined 15 min after coitus, many spermatozoa were around the opening of the uterotubal junction. Spermatozoa that entered the uterotubal junction were seemingly not moving, yet they steadily migrated toward the isthmus at a speed only time-lapse video recording could demonstrate. Many spermatozoa reaching the lower isthmus were motile. The site where spermatozoa attached and detached from the isthmus epithelium shifted from the lower to the upper segment of the isthmus with time. Virtually all the live spermatozoa within the lower isthmus were acrosome intact, whereas many of the actively motile spermatozoa in the upper isthmus were acrosome reacted. As far as we could observe, all the spermatozoa we found within the lumen of the ampulla and the cumulus oophorus were acrosome reacted. Even though we saw only a very few spermatozoa within the ampulla during fertilization, all were associated with, or were already within, oocytes, indicating that mouse fertilization in vivo is extremely efficient.

Expression of TEX101, regulated by ACE, is essential for the production of fertile mouse spermatozoa.

Formation of spermatozoa of normal shape, number, and motility is insufficient for the male siring of pups. The spermatozoa must be accompanied by sound fertilizing ability. We found that males with disrupted testis-expressed gene 101 (Tex101) produce normal-looking but fertilization-incompetent spermatozoa, which were accompanied by a deficiency of a disintegrin and metallopeptidase domain 3 (ADAM3) on sperm plasma membrane. It was also found that the existence of TEX101 on spermatozoa was regulated by angiotensin-converting enzyme (ACE). The removal of GPI-anchored protein TEX101 by ACE was essential to produce fertile spermatozoa, and the function of ACE was not depending on its well-known peptidase activity. The finding of TEX101 as a unique specific substrate for ACE may provide a potential target for the production of an awaited contraceptive medicine for men.

Function of the acrosomal matrix: zona pellucida 3 receptor (ZP3R/sp56) is not essential for mouse fertilization.

In mammalian fertilization, sperm-zona pellucida binding is considered to be a critical aspect of gamete interaction. In this study, we examine the mouse sperm acrosomal matrix protein zona pellucida 3 receptor (ZP3R; formerly called sp56) because of our interest in defining the function of the acrosomal matrix, the particulate compartment within the sperm secretory acrosome. Using targeted deletion of the Zp3r gene by homologous recombination, we examined the fertility of nullizygous animals. Our experiments showed that males and females homozygous for the affected gene exhibited no differences in litter sizes compared to wild-type and heterozygous animals. Testis weights of nullizygous males were equivalent to those of wild-type and heterozygous males, and no differences in the number of sperm produced by mice of three genotypes were found. In vitro fertilization rates using cumulus-intact and cumulus-free oocytes were also equivalent. Examination of sperm-binding zonae of unfertilized eggs and the ability of the sperm to undergo acrosomal exocytosis in response to calcium ionophore A23187 displayed no differences between wild-type, heterozygous, and nullizygous mouse sperm. These results provide further evidence that either ZP3R is not involved in sperm-zona pellucida binding or this process might be functionally redundant, involving multiple proteins for gamete interactions.

Cerebrospinal Fluid Leakage to the Chest Subcutaneous Pocket Due to Aggressive Brain Edema around the Leads for Deep Brain Stimulation: A Case Report and Literature Review.

Cerebral edema around the lead has been reported as a complication of deep brain stimulation; however, the causes remain unknown. Herein, we present a rare case of sudden cerebral edema around the lead occurring after deep brain stimulation. This was accompanied by cerebrospinal fluid (CSF) leakage into the subcutaneous thoracic pocket around the implantable pulse generator in a 53-year-old man with Parkinson's disease. No such case has been reported thus far. Lumbar drainage was performed to improve CSF leakage. The cerebral edema initially responded to steroids, but then it stopped responding to treatment. The edema appeared alternately on the left and right sides, and cyst formation was noted around the left lead. There are some reports of cyst formation around the lead; however, in our case, images were used to monitor the edema and cyst from their appearance to their disappearance. Our data suggest that cyst formation and cerebral edema are related.

Foreign body granuloma around implantable pulse generator for deep brain stimulation: Two case reports.

We report two cases of granuloma that occurred around an implantable pulse generator (IPG) for deep brain stimulation. Both cases showed no signs of infection and disappeared after moving the IPG and removing the granulation. If a noninfectious mass is formed, the relocation of IPG may improve it.

Mechanisms of fertilization--a view from the study of gene-manipulated mice.

Recent gene knockout approaches have revealed that many of the factors previously considered to be important were largely dispensable in gene-knockout animals, and that previously unknown factors are emerging. Unexpectedly, sperm from 5 different gene-disrupted mouse lines (calmegin (Clgn), Adam1a, Adam2, Adam3, and Ace) all have defective zona-binding ability and oviduct-migrating ability. We have disrupted a new testis-specific molecular chaperone, calsperin (Calr3), which became the sixth gene sharing the same infertile phenotype. The relationships among these 6 factors are discussed. After zona penetration, sperm needs to fuse with eggs. We reported that sperm require IZUMO1 and eggs require CD9 for sperm-egg fusion. However, the distribution of IZUMO1 is not limited to the equatorial segment where it is believed the fusion takes place. Therefore, we produced a mouse line that lacks an equatorial segment-specific antigen, Spesp1. The Spesp1 +/- and -/- sperm showed a decreased fusing ability compared with wild-type sperm, but the cause of the impaired fusion may not directly relate to the mechanism involving IZUMO1. In order to study the mechanism of fertilization, the visualization of sperm in vivo provides a powerful tool. We made a new transgenic mouse line that produces sperm with green fluorescent protein-tagged acrosome and DSRed2-tagged mitochondria. Studies of fertilization using gene-manipulated animals are described in the present review.

Transgenic mouse sperm that have green acrosome and red mitochondria allow visualization of sperm and their acrosome reaction in vivo.

In the present paper, we introduce a transgenic mouse line whose sperm express green fluorescent protein (GFP) in their acrosome and red fluorescent protein (RFP) in their mitochondria [B6D2F1- Tg(CAG/su9-DsRed2, Acr3-EGFP)RBGS002Osb]. The dual fluorescent sperm showed normal fertilizing ability in both in vivo and in vitro fertilization and the sperm could be observed through uterine and oviductal walls when female reproductive tracts were dissected out and placed under excitation light. This characteristic could facilitate examination of sperm migration inside the female reproductive tract as well as facilitating in situ live imaging of the acrosome reaction, the details of which have remained elusive.

Disruption of ADAM3 impairs the migration of sperm into oviduct in mouse.

Sperm from four different gene-disrupted mouse lines (calmegin [Clgn], Adam1a, Adam2, and Ace) are known to have defective zona-binding ability. Moreover, it is also reported that the sperm from all of these mouse lines exhibit another common phenotype of impaired migration into oviduct despite the large number of sperm found in uterus after coitus. On the other hand, the sperm from the Adam3-disrupted mouse line was reported to have defects in binding ability to zona, but were able to move into the oviduct. In order to clarify the difference, we investigated the migration of ADAM3-null sperm into oviduct precisely by visualizing the sperm by using acrosin-green fluorescent protein as a tag. As a result, in contrast to previous observations, it was demonstrated that the Adam3-disrupted sperm were unable to migrate into the oviduct after coitus. It was ultimately shown that, in five out of five different gene-disrupted mouse lines, the phenotype of impaired sperm binding to zona pellucida was accompanied by the loss of ability of sperm to migrate into the oviduct. This indicates a close relationship between the two phenomena, and also that sperm migration into the oviduct is a crucial step for fertilization.