Antti A. Aarnisalo

NEUROPEPTIDE FF, A MAMMALIAN NEUROPEPTIDE WITH MULTIPLE FUNCTIONS

Neuropeptide FF (NPFF) and neuropeptide AF (NPAF) are two mammalian amidated neuropeptides which are highly concentrated in the posterior pituitary, spinal cord, hypothalamus and medulla. One precursor protein has been identified in mouse, rat, bovine and human brain. The precursor contains a single copy of both peptides, followed by a glycine residues necessary for amidation and flanked by basic residues necessary for processing by enzymes. In the brain, NPFF-like immunoreactive neurons are found in the hypothalamus and medulla. These systems may be associated with observed effects of NPFF on memory and autonomic regulation, respectively. A hypothalamo-pituitary pathway may be involved in neuroendocrine regulation. This is supported by lack of NPFF in the pituitary gland of vasopressin-deficient Brattleboro rats. It is also possible that NPFF acts as a hormone, as it has been detected in human plasma. The spinal cord contains an intrinsic NPFF-ir neuron system, with cell bodies in the dorsal horn and around the central canal. Nerve terminals are highly concentrated in the superficial laminae of the dorsal horn, where NPFF-immunoreactivity can be released by, e.g., potassium and substance P. One specific high-affinity binding site, distinct from binding sites for other peptides, has been characterized in the rat and human brain and spinal cord. The NPFF receptor appears to be coupled to a G-protein, but details of the second messenger systems have not been clarified yet. Intracerebroventricular injection of NPFF induces a vigorous abstinence syndrome in morphine-tolerant rats. Although clear antiopioid-like effects of NPFF on pain have been observed, some studies have also demonstrated long-lasting analgesic effects. These findings and the observed increase in NPFF-immunoreactivity in the cerebrospinal fluid during development of opiate tolerance render NPFF an interesting and challenging target of investigation.

Long-term hearing results after stapes surgery: a 20-year follow-up.

Objective The aim of this study was to evaluate the results of stapes surgery after 20 years of follow-up and to compare the results between large fenestra versus small fenestra stapedotomy. Study Design Retrospective clinical study. Setting Tertiary referral center (university hospital). Patients One hundred forty-two patients with otosclerosis treated by surgery. Intervention Eighty patients had a total stapedectomy with House-wire prosthesis and 62 patients a stapedotomy with Teflon-piston prosthesis. Main Outcome Measures Preoperative, postoperative, and long-term hearing thresholds were compared. Patients filled in a questionnaire about the impact of surgery on the quality of life and postoperative symptoms. Results The long-term pure tone average improvement did not differ significantly between the techniques compared with the preoperative values. The air-bone gap tended to enlarge as a function of time. The change in the pure tone average was 0.9 dB per year for both techniques. In the questionnaire, some patients reported vertigo, tinnitus, loud noise intolerance, and taste disturbances. Loud noise intolerance seemed to persist in the long term. Surgery had no effect on preoperative tinnitus. Conclusions There were no statistically significant differences between the techniques regarding hearing results. Over the long term, both techniques are safe and effective in restoring hearing and improving quality of life.

Neuropeptide FF in the Rat Spinal Cord During Carrageenan Inflammation

The role of neuropeptide FF (NPFF) in the modulation of spinal nociception was studied in rats with carrageenan inflammation in the hind paw. Normally no NPFF-ir neuronal cell bodies are found in the spinal cord. During inflammation NPFF-neurons were seen in an area receiving innervation from the inflamed hind limb, but in rats pretreated with morphine no NPFF-ir neurons were found. NPFF or IgG from NPFF immunoserum administered intrathecally had no effect in thermal and mechanical nociceptive tests. Morphine produced significant antinociception in both tests in the inflamed paw, but the effect was not modified by NPFF. These findings differ from the effects of intrathecal administration of NPFF and opioids in acute thermal tests when no inflammation is present. The role of NPFF in the modulation of nociception in the spinal cord may be markedly changed during acute inflammation.

Magnetic resonance imaging findings in the auditory pathway of patients with sudden deafness.

Objectives: The objectives of this study were to evaluate magnetic resonance imaging (MRI) findings of patients with sudden sensorineural hearing loss (SSNHL) and to grade the findings based on their clinical importance. Study Design: A prospective clinical study. Setting: A tertiary referral center (university hospital). Patients: MRI findings of 82 consecutive patients with SSNHL fulfilling the inclusion criteria. Main Outcome Measures: We studied 1.0-T MR images that were analyzed by one experienced neuroradiologist. Results: Of the six cases (7%) in which clearly hearing loss was obviously associated with the observed pathology, four patients had an acoustic neuroma in the internal auditory canal or cerebellopontine angle, one patient had changes at the level of pons, and one patient had an obliterated internal carotid artery. Of the six other patients (7%) in which MRI revealed changes that suggest a possible etiology to hearing loss, two patients showed a demyelinating process and four patients showed blood vessel abnormalities such as caroticocavernous fistula, abnormally locating vertebral or basilar artery, and a venous angioma. Conclusions: Enhanced MR imaging seems to be a useful examination in patients with SSNHL. The aim should not be only to exclude specific retrocochlear etiologies, but by appropriate techniques, MRI could reveal both peripheral and central abnormalities.

Apoptosis in auditory brainstem neurons after a severe noise trauma of the organ of Corti: intracochlear GDNF treatment reduces the number of apoptotic cells.

We have studied the morphological and cellular changes in the cochlear nucleus (CN) after cochlear nerve degeneration and whether these changes can be prevented by rescuing the primary cochlear neurons from degeneration with local glial cell line derived neurotrophic factor (GDNF) treatment. Degeneration of spiral ganglion neurons was seen to lead to a reduction of the volume of the anteroventral cochlear nucleus (AVCN); the size of the cell nuclei in the AVCN also was reduced. No differences were observed in cell density. After intrascalar GDNF treatment the volume of the AVCN was significantly larger when compared to the untreated side, and the size of the cell nuclei in the AVCN was significantly larger on the treated side. After degeneration of spiral ganglion neurons, an increased number of apoptotic cell nuclei were seen in ipsilateral CN and superior olivary complex. This increase was significantly smaller after intrascalar GDNF treatment. Degeneration of primary cochlear neurons seems to lead to an increase in the number of CN neurons undergoing apoptotic cell death. This can be prevented partially by rescuing primary cochlear neurons from degeneration with local GDNF treatment.

Transcutaneous vagus nerve stimulation in tinnitus: a pilot study

Abstract Conclusions: This pilot study shows that transcutaneous vagus nerve stimulation (tVNS), if combined with sound therapy (ST), reduces the severity of tinnitus and tinnitus-associated distress. Our magnetoencephalography (MEG) results show that auditory cortical activation can be modulated by the application of tVNS. Thus, tVNS might offer a new avenue to treat tinnitus and tinnitus-associated distress. Objectives: Recent studies suggest that tinnitus can be improved by tailored ST or by VNS plus ST. Our aims were to study whether tVNS has therapeutic effects on patients with tinnitus and, additionally, if tVNS has effects on acoustically evoked neuronal activity of the auditory cortex. Methods: The clinical efficacy was studied by a short-term tVNS plus ST trial in 10 patients with tinnitus using disease-specific and general well-being questionnaires. tVNS was delivered to the left tragus. The acute effects of tVNS were evaluated in eight patients in the MEG study in which the N1m response was analyzed in terms of source level amplitude and latency in the presence or absence of tVNS. Results: The treatment with tVNS plus ST produced improved mood and decreased tinnitus handicap scores, indicating reduced tinnitus severity. The application of tVNS decreased the amplitude of auditory N1m responses in both hemispheres.

Plasticity of histamine H 3 receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat

BackgroundIn rat, deafferentation of one labyrinth (unilateral labyrinthectomy) results in a characteristic syndrome of ocular and motor postural disorders (e.g., barrel rotation, circling behavior, and spontaneous nystagmus). Behavioral recovery (e.g., diminished symptoms), encompassing 1 week after unilateral labyrinthectomy, has been termed vestibular compensation. Evidence suggesting that the histamine H3 receptor plays a key role in vestibular compensation comes from studies indicating that betahistine, a histamine-like drug that acts as both a partial histamine H1 receptor agonist and an H3 receptor antagonist, can accelerate the process of vestibular compensation.ResultsExpression levels for histamine H3 receptor (total) as well as three isoforms which display variable lengths of the third intracellular loop of the receptor were analyzed using in situ hybridization on brain sections containing the rat medial vestibular nucleus after unilateral labyrinthectomy. We compared these expression levels to H3 receptor binding densities.Total H3 receptor mRNA levels (detected by oligo probe H3X) as well as mRNA levels of the three receptor isoforms studied (detected by oligo probes H3A, H3B, and H3C) showed a pattern of increase, which was bilaterally significant at 24 h post-lesion for both H3X and H3C, followed by significant bilateral decreases in medial vestibular nuclei occurring 48 h (H3X and H3B) and 1 week post-lesion (H3A, H3B, and H3C). Expression levels of H3B was an exception to the forementioned pattern with significant decreases already detected at 24 h post-lesion. Coinciding with the decreasing trends in H3 receptor mRNA levels was an observed increase in H3 receptor binding densities occurring in the ipsilateral medial vestibular nuclei 48 h post-lesion.ConclusionProgressive recovery of the resting discharge of the deafferentated medial vestibular nuclei neurons results in functional restoration of the static postural and occulomotor deficits, usually occurring within a time frame of 48 hours in rats. Our data suggests that the H3 receptor may be an essential part of pre-synaptic mechanisms required for reestablishing resting activities 48 h after unilateral labyrinthectomy.

Efficiency of hyperbaric oxygen therapy in experimental acute acoustic trauma from firearms.

In acute acoustic trauma (AAT), excessive noise exposure causes rupture of cell membranes and decreased cochlear blood flow. This leads to decreased oxygen tension in inner ear fluids and reduction of a variety of different oxygen-dependent cellular activities. Hyperbaric oxygen treatment (HBO) may help the cells suffering from hypoxia to survive. We exposed male Wistar rats to 60 impulses of 162-dB SPL from a 7.62-mm assault rifle equipped with a blank adaptor. After the exposure, 15 animals were given HBO treatment for 90 min daily for 10 consecutive days at 0.25 MPa. After a survival time of 4 weeks, auditory brainstem responses were measured and the left cochleae processed for light microscopy. The impulse noise caused permanent damage to the cochlea of all animals, with the most severe lesions in the lower middle coil, where a significantly smaller number of hair cells was missing in the HBO-treated group. The morphological damage was also reflected in function, as measured by auditory brainstem responses, which showed the greatest threshold shifts at 6.0, 8.0 and 10.0 kHz.In acute acoustic trauma (AAT), excessive noise exposure causes rupture of cell membranes and decreased cochlear blood flow. This leads to decreased oxygen tension in inner ear fluids and reduction of a variety of different oxygen-dependent cellular activities. Hyperbaric oxygen treatment (HBO) may help the cells suffering from hypoxia to survive. We exposed male Wistar rats to 60 impulses of 162-dB SPL from a 7.62-mm assault rifle equipped with a blank adaptor. After the exposure, 15 animals were given HBO treatment for 90 min daily for 10 consecutive days at 0.25 MPa. After a survival time of 4 weeks, auditory brainstem responses were measured and the left cochleae processed for light microscopy. The impulse noise caused permanent damage to the cochlea of all animals, with the most severe lesions in the lower middle coil, where a significantly smaller number of hair cells was missing in the HBO-treated group. The morphological damage was also reflected in function, as measured by auditory brainstem responses, which showed the greatest threshold shifts at 6.0, 8.0 and 10.0 kHz.

Mastoid Biofilm in Chronic Otitis Media

Hypothesis We designed a study to determine the role of mastoid mucosal biofilm in chronic otitis media (COM). Background Biofilm formation has been found in several chronic airway infections. COM is associated with chronic, recalcitrant infection of the mastoid mucosa, and surgery often is required. Methods COM patients were divided into 2 groups: one with chronic suppurative otitis media (CSOM) and one with cholesteatoma presence. All COM patients had mastoid involvement in a preoperative computed tomographic scan. The control group consisted of patients undergoing cochlear implantation, with no previous history of chronic otitis media. Mastoid mucosa samples were harvested during mastoidectomy. The samples were studied with multiplex-polymerase chain reaction and with CSLM using BacLight Live/Dead stain. Routine bacterial culture was performed in selected cases. Results A total of 29 COM patients underwent mastoidectomy. Mastoid mucosal biofilm formation could be found in 19 (66%) of these patients. In the control group, there were 11 cases of cochlear implantation, and 1 patient (9%) presented mastoid mucosal biofilm. In the cholesteatoma group, there were 17 patients, of which, 14 (82%) presented biofilm, whereas in the CSOM group, 5 (42%) of 12 patients presented biofilm. The correlation between COM and biofilm was statistically significant (Fisher’s exact test, p = 0.003), as was the correlation between cholesteatoma and biofilm, in comparison with the CSOM group (Fisher’s exact test, p = 0.046). Conclusion Mastoid mucosal biofilm could be seen in patients with COM with or without cholesteatoma. The role of mastoid biofilm in the development of cholesteatoma should be studied further.

The development and evaluation of the Finnish Matrix Sentence Test for speech intelligibility assessment

Abstract Conclusion: The Finnish Matrix Test is the first sentence test in noise for the Finnish language. It was developed according to the HearCom standards and provides reliable speech intelligibility measurements with highly comparable results with the other international matrix tests. Objectives: The aim of the study was to develop an accurate speech intelligibility test in noise for the Finnish language that is comparable across different languages. Methods: We chose a matrix sentence test, which comprises a base matrix of 10 names, verbs, numerals, adjectives and nouns. Test lists were formed from this matrix quasi randomly, providing test sentences of the same syntactical structure. The speech material corresponds to everyday spoken language and the phoneme distribution is representative of the Finnish language. The test was optimized by determining the speech recognition thresholds of the individual words and subsequently by applying level corrections of up to ±3 dB. Evaluation measurements were performed to check the equivalence of the different test lists with respect to speech intelligibility and to provide reference values for further clinical applications. Results: After training, the mean speech recognition threshold (SRT) and the slope of the final test lists were –10.1 ± 0.1 dB signal-to-noise-ratio (SNR)and 16.7 ± 1.2%/dB, respectively (measurements at constant level; inter-list variability). The mean SRT and the slope of the test subjects were –10.1 ± 0.7 dB SNR and 17.5 ± 2.2%/dB (measurements at constant level; inter-subject variability). The expected SRT range for normal-hearing young adults for adaptive measurements is –9.7 ± 0.7 dB SNR.