Trauma In Guinea Pig Research Articles

Assessment of the efficacy of a local steroid rescue treatment administered 2 days after a moderate noise-induced trauma in guinea pig

Objectives: Intratympanic injection of corticosteroids membrane after noise-induced hearing loss is an accepted alternative to general administration. We investigated the effect on hearing of a hyaluronic acid gel with liposomes loaded with dexamethasone (DexP) administered into the middle ear.Methods: An acute acoustic trauma was performed to 13 guinea pigs for a period of 1 h on Day −2. Two 2 days after the noise trauma, the animals were then assigned randomly to four experimental groups: control without gel, gel injection, gel-containing free DexP, gel-containing DexP loaded into liposomes. Auditory thresholds were measured with Auditory Brainstem Response before Day −2 and at Day 0, Day 7 and Day 30 after noise trauma.Results: Seven days after, a complete hearing recovery was observed in the control group at all frequencies apart from 8 kHz, and no recovery was observed in the three groups receiving a gel injection. Thirty days after trauma, all of the animals had recovered normal hearing, apart from at the 8-kHz frequency, with similar auditory thresholds.Conclusions: Local DexP administration 48 h after a mild acoustic trauma did not improve hearing recovery, even with a sustained release in a specific gel formulation designed for inner ear therapy.

Effects of pulsatile electrical stimulation of the round window on central hyperactivity after cochlear trauma in guinea pig

Partial hearing loss induced by acoustic trauma has been shown in animal models to result in an increased spontaneous firing rate in central auditory structures. This so-called hyperactivity has been suggested to be involved in the generation of tinnitus, a phantom auditory sensation. Although there is no universal cure for tinnitus, electrical stimulation of the cochlea, as achieved by a cochlear implant, can result in significant reduction of the tinnitus percept. However, the mechanism by which this tinnitus suppression occurs is as yet unknown and furthermore cochlear implantation may not be an optimal treatment option for tinnitus sufferers who are not profoundly deaf. A better understanding of the mechanism of tinnitus suppression by electrical stimulation of the cochlea, may lead to the development of more specialised devices for those for whom a cochlear implant is not appropriate. This study aimed to investigate the effects of electrical stimulation in the form of brief biphasic shocks delivered to the round window of the cochlea on the spontaneous firing rates of hyperactive inferior colliculus neurons following acoustic trauma in guinea pigs. Effects during the stimulation itself included both inhibition and excitation but spontaneous firing was suppressed for up to hundreds of ms after the cessation of the shock train in all sampled hyperactive neurons. Pharmacological block of olivocochlear efferent action on outer hair cells did not eliminate the prolonged suppression observed in inferior colliculus neurons, and it is therefore likely that activation of the afferent pathways is responsible for the central effects observed.

Valproic Acid Increases Formation of ROS and Interferes with Hearing Recovery after Noise Trauma in Guinea Pigs

Department of Otolaryngology Head and Neck Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea (SL, YBC, HHC ) Department of Physiology, Chonnam National University Medical School, Gwangju, Republic of Korea (HSJ, CMK, SJ, JSP) Research Institute of Medical Sciences, Chonnam National University, Gwangju, Republic of Korea (HSJ, CMK, SJ, JSP, SL, YBC, HHC) *: These authors equally contributed to this work.

Application of a TNF-alpha-inhibitor into the scala tympany after cochlear electrode insertion trauma in guinea pigs: Preliminary audiologic results

Objective: Cochlear implantation trauma causes both macroscopic and inflammatory trauma. The aim of the present study was to evaluate the effectiveness of the TNF-alpha inhibitor etanercept applied after cochlear implantation trauma on the preservation of acoustic hearing. Design: Guinea pigs were randomly assigned to three groups receiving cochlear implantation trauma by cochleostomy. In one group, the site was sealed by bone cement with no further treatment. A second group was additionally implanted with an osmotic minipump delivering artificial perilymph into the scala tympani for seven days. In the third group, etanercept 1 mg/ml was added to artificial perilymph. Hearing was assessed by auditory brainstem responses at 2, 4, 6, and 8 kHz prior to and after surgery and on days 3, 5, 7, 14, 28. Study sample: Fifteen healthy guinea pigs. Results: The trauma led to threshold shifts from 50.3 dB ± 16.3 dB to 68.0 dB ± 19.3 dB. Hearing thresholds were significantly lower in etanercept-treated animals compared to controls on day 28 at 8 kHz and from day 3 onwards at 4 and 2 kHz (p < 0.01; two-way RM ANOVA / Bonferroni t-test). Conclusion: The application of etanercept led to preservation of acoustic hearing after cochlear implantation trauma.

Changes in Inner Ear Structure and Function after Drill - Induced Acoustic Trauma

Background: drilling on the intact ossicular chain produce acoustic trauma resulting in inner ear structure damage, these changes occurred in organ of corti with disruption of cytoarchitecture and cellular degeneration. Objective: To evaluate the changes in inner ear structure and function after drill - induced acoustic trauma in guinea pigs by Scanning Electron Microscope (SEM) and Otoacoustic emission (OAE). Methods and Material: An experimental study conducted on healthy pigmented guinea pigs in Otolaryngology-Head and neck Surgery Department at Jazan University, Kingdom of Saudi Arabia. Results: Thirty guinea pigs were divided into a control group (N) to document the baseline Distortion Product Otoacoustic Emissions (DPOAEs) and the normal scanning electron microscopic (SEM) morphology of the inner ear, Drill induced acoustic trauma group (D) to evaluate the effect of induced sensorineural hearing loss using micromotor drill (20,000rpm) maximum speed against the body of incus and 2weeks postoperative group (2W) to evaluate to the effect of spontaneous recovery after 2 weeks from induced sensorineural hearing loss which showed spontaneous although incomplete recovery of the DPOAEs amplitudes and SEM morphology with scar tissue replacing the damaged outer hair cells. Conclusion: Avoid touching ossicular chain when using high speed drill during ear surgery as this may cause structural and functional damage to the inner ear. Spontaneous recovery could be occurs after acoustic trauma but incomplete recovery with permanent scar formation in outer hair cells may occur.

Effects of chronic furosemide on central neural hyperactivity and cochlear thresholds after cochlear trauma in Guinea pig.

Increased neuronal spontaneous firing rates have been observed throughout the central auditory system after trauma to the cochlea and this hyperactivity is believed to be associated with the phantom perception of tinnitus. Previously, we have shown in an animal model of hearing loss, that an acute injection with furosemide can significantly decrease hyperactivity after cochlear trauma and eliminate behavioral evidence of tinnitus of early onset. However, furosemide also has the potential to affect cochlear thresholds. In this paper, we measured the effects of a chronic (daily injections for 7 days) furosemide treatment on the spontaneous firing rate of inferior colliculus neurons and on cochlear thresholds in order to establish whether a beneficial effect on hyperactivity can be obtained without causing additional hearing loss. Guinea pigs were exposed to a 10–kHz, 124 dB, 2 h acoustic trauma, and after 5 days of recovery, were given daily i.p. injections of 80 mg/kg furosemide or an equivalent amount of saline. The activity of single IC neurons was recorded 24 h following the last injection. The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus. These results that suggest a long-term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.

Effects of furosemide on cochlear neural activity, central hyperactivity and behavioural tinnitus after cochlear trauma in guinea pig.

Cochlear trauma causes increased spontaneous activity (hyperactivity) to develop in central auditory structures, and this has been suggested as a neural substrate for tinnitus. Using a guinea pig model we have previously demonstrated that for some time after cochlear trauma, central hyperactivity is dependent on peripheral afferent drive and only later becomes generated intrinsically within central structures. Furosemide, a loop diuretic, reduces spontaneous firing of auditory afferents. We investigated in our guinea pig model the efficacy of furosemide in reducing 1) spontaneous firing of auditory afferents, using the spectrum of neural noise (SNN) from round window recording, 2) hyperactivity in inferior colliculus, using extracellular single neuron recordings and 3) tinnitus at early time-points after cochlear trauma. Tinnitus was assessed using gap prepulse inhibition of acoustic startle (GPIAS). Intraperitoneal furosemide, but not saline, caused a marked decrease in both SNN and central hyperactivity. Intracochlear perfusion with furosemide similarly reversed central hyperactivity. In animals in which GPIAS measurements suggested the presence of tinnitus (reduced GPIAS), this could be reversed with an intraperitoneal injection with furosemide but not saline. The results are consistent with furosemide reducing central hyperactivity and behavioural signs of tinnitus by acting peripherally to decrease spontaneous firing of auditory afferents. The data support the notion that hyperactivity may be involved in the generation of tinnitus and further suggest that there may be a therapeutic window after cochlear trauma using drug treatments that target peripheral spontaneous activity.

Does Vestibular End-Organ Function Recover after Gentamicin-Induced Trauma in Guinea Pigs?

Until 1993 it was commonly accepted that regeneration of vestibular hair cells was not possible in mammals. Two histological studies then showed structural evidence for spontaneous regeneration of vestibular hair cells after gentamicin treatment. There is less evidence for functional recovery going along with this regenerative process; in other words, do regenerated hair cells function adequately? This study aims to address this question, and in general evaluates whether spontaneous functional recovery may occur, in the short or long term, in mammals after ototoxic insult. Guinea pigs were treated with gentamicin for 10 consecutive days at a daily dose of 125 mg/kg body weight. Survival times varied from 1 day to 16 weeks. Vestibular short-latency evoked potentials (VsEPs) to linear acceleration pulses were recorded longitudinally to assess otolith function. After the final functional measurements we performed immunofluorescence histology for hair cell counts. Auditory brainstem responses (ABRs) to click stimuli were recorded to assess cochlear function. As intended, gentamicin treatment resulted in significant loss of utricular hair cells and accompanying declines in VsEPs. Hair cell counts 8 or 16 weeks after treatment did not significantly differ from counts after shorter survival periods. Maximal functional loss was achieved 1-4 weeks after treatment. After this period, only 2 animals showed recovery of VsEP amplitude - all other animals did not reveal signs of regeneration or recovery. In contrast, after initial ABR threshold shifts there was a small but significant recovery. We conclude that spontaneous recovery of otolith function, in contrast to cochlear function, is very limited in guinea pigs. These results support the concept of intratympanic gentamicin treatment where gentamicin is used for chemoablation of the vestibular sensory epithelia.

The effect of caffeine on hearing in a guinea pig model of acoustic trauma

ObjectiveCaffeine is a widely consumed substance affecting the metabolism of adenosine and cellular metabolism of calcium. Noise also affects these metabolic pathways while inducing hearing loss. The aim of this study was to determine the effect of daily intake of caffeine on hearing loss after an episode of acoustic trauma in guinea pigs. Materials and methodsIn this pilot study, forty guinea pigs were randomly divided into four groups: group I (control, n=10) received intraperitoneal saline, group II (n=10) received intraperitoneal caffeine (120mg/kg/day) for 14days, group III (n=10) was exposed to noise (tone of 6kHz at 120dB for one hour) and group IV (n=10) was exposed to noise as group III and received caffeine as group II. Auditory brainstem responses were measured at four different frequencies (8, 16, 20, and 25kHz) prior to and at intervals of 1h, 3days, 10days, and 14days after the initial treatment. On day 14, morphological analysis was performed to assess the effects of caffeine on acoustic trauma. ResultsAggravated hearing loss was observed in group IV after 10days of follow-up. After 14days, one of the four frequencies (8kHz) tested showed statistically significant greater impairment in hearing (8.2±3.6dB, p=0.026). Auditory hair cells showed no difference while spiral ganglion cell counts were diminished in group IV (p<0.05). ConclusionThese findings indicate that caffeine may have a detrimental effect on hearing recovery after a single event of acoustic trauma.

Effects of Carbogen on Cochlear Blood Flow and Hearing Function Following Acute Acoustic Trauma in Guinea Pigs

Disturbances of microcirculation and hemorheological changes in the inner ear are the results of noise-induced hearing loss (NIHL). Both the disturbances of microcirculation and hemorheological changes are the etiologies of NIHL development, but they are also the results. Although previous reports that inhalation of high concentration of CO(2) may increase cochlear blood flow (CoBF), the effects of carbogen on the cochlear microcirculation and NIHL remain unclear. Changes induced by noise, carbogen and pure oxygen within the cochlear lateral wall microvasculature and in hearing thresholds were observed in guinea pigs using intravital microscopy and the auditory brainstem response. At the same time, arterial oxygen saturation and morphologic changes of cochlear hair cells were observed. Carbogen inhalation increased vessel diameters and blood flow velocities. Hearing thresholds elevation in the carbogen group was smaller than those in the control and oxygen group (p <0.05). Carbogen inhalation produced a trend toward less threshold shift after noise exposure, which reached statistical significance after day 3 (p <0.01). Respiratory acidosis was not found in our study. The segmented basal membranes of Corti in three groups indicated that no losses or discorders of hair cells were found. Carbogen inhalation can preserve hearing in animal models after acute acoustic trauma.

Follow-up of latency and threshold shifts of auditory brainstem responses after single and interrupted acoustic trauma in guinea pig

Thresholds of auditory brainstem responses (ABRs) are widely used to estimate the level of noise-induced hearing loss or the level of acquired resistance to acoustic trauma after repeated exposures, i.e., the “toughening” effect. Less is known about ABR latencies and their relation to threshold changes. Guinea pigs were exposed to a traumatic pure tone at 5 kHz, 120 dB SPL, as either single (2 h, 4 h) or repeated (1 h every 48 h, four times) sessions. Thresholds and latencies of ABRs were monitored up to 45 days following the acoustic trauma. We show that latencies are prolonged in the case of large temporary threshold shifts observed in the days following trauma. The latency shift decreases after several repeated exposures, then stabilizes, similar to thresholds, suggesting that the “toughening” effect also applies to latencies. Permanent latency shift is usually very small compared to the permanent threshold shift. This effect could produce a recovery in the ability to process auditory information through the precise timing of neuronal events. Our study indicates that when estimated at suprathreshold stimulation level (70 dB SPL), latency provides complementary information to the sole threshold.

D-JNKI-1 Treatment Prevents the Progression of Hearing Loss in a Model of Cochlear Implantation Trauma

Hypotheses: 1) Hearing loss caused by electrode insertion trauma has both acute and delayed components; and 2) the delayed component of trauma-initiated hearing loss can be prevented by a direct delivery of a peptide inhibitor of the c-Jun N-terminal kinase cell death signal cascade, that is, D-JNKI-1, immediately after the electrode insertion within the cochlea. Background: Acute trauma to the macroscopic elements of the cochlea from electrode insertion is well known. The impact of trauma-induced oxidative stress within injured cochlear tissues and the efficacy of drugs (e.g., D-JNKI-1) to prevent apoptosis of damaged hair cells is not well defined. Methods: Hearing function was tested by pure-tone evoked auditory brainstem responses (ABRs) and distortion products of otoacoustic emissions (DPOAEs). D-JNKI-1 in artificial perilymph (AP) or AP alone was delivered into the scala tympani immediately after electrode trauma and for 7 days. Controls were nontreated contralateral and D-JNKI-1-treated ears without electrode insertion trauma. Results: There was no increase in the hearing thresholds of either the contralateral control ears or in the D-JNKI-1 without trauma animals. There was a progressive increase in ABR thresholds and decrease in DPOAE amplitudes after electrode insertion trauma in untreated and in AP-treated cochleae. Treatment with D-JNKI-1 prevented the progressive increase in ABR thresholds and decrease in DPOAE amplitudes that occur after electrode insertion trauma. Conclusion: Hearing loss caused by cochlear implant electrode insertion trauma in guinea pigs has both acute and delayed components. The delayed component can be prevented by treating the cochlea with D-JNKI-1.

D-JNKI-1 Treatment Prevents the Progression of Hearing Loss in a Model of Cochlear Implantation Trauma

1) Hearing loss caused by electrode insertion trauma has both acute and delayed components; and 2) the delayed component of trauma-initiated hearing loss can be prevented by a direct delivery of a peptide inhibitor of the c-Jun N-terminal kinase cell death signal cascade, that is, D-JNKI-1, immediately after the electrode insertion within the cochlea. Acute trauma to the macroscopic elements of the cochlea from electrode insertion is well known. The impact of trauma-induced oxidative stress within injured cochlear tissues and the efficacy of drugs (e.g., D-JNKI-1) to prevent apoptosis of damaged hair cells is not well defined. Hearing function was tested by pure-tone evoked auditory brainstem responses (ABRs) and distortion products of otoacoustic emissions (DPOAEs). D-JNKI-1 in artificial perilymph (AP) or AP alone was delivered into the scala tympani immediately after electrode trauma and for 7 days. Controls were nontreated contralateral and D-JNKI-1-treated ears without electrode insertion trauma. There was no increase in the hearing thresholds of either the contralateral control ears or in the D-JNKI-1 without trauma animals. There was a progressive increase in ABR thresholds and decrease in DPOAE amplitudes after electrode insertion trauma in untreated and in AP-treated cochleae. Treatment with D-JNKI-1 prevented the progressive increase in ABR thresholds and decrease in DPOAE amplitudes that occur after electrode insertion trauma. Hearing loss caused by cochlear implant electrode insertion trauma in guinea pigs has both acute and delayed components. The delayed component can be prevented by treating the cochlea with D-JNKI-1.

Post-exposure administration of edaravone attenuates noise-induced hearing loss

We investigated the effects of the antioxidant edaravone against acoustic trauma in guinea pigs. Edaravone (1.722 × 10 − 2 M) was infused into the right ear by an osmotic pump, and the left ear was untreated for control. Animals received edaravone 9 h before (− 9 h group, n = 7) and 9 h (+ 9 h group, n = 8), 21 h (+ 21 h group, n = 7) and 33 h (+ 33 h group, n = 4) after 3-h exposure to 130-dB noise. Seven days after noise exposure, we examined the shift in auditory brainstem response thresholds and histopathologic characteristics of the sensory epithelia. The smallest shift in auditory brainstem response threshold and smallest proportion of missing outer hair cells were observed in the + 9 h group. This result was supported by immunohistochemical analysis of 4-hydroxy-2-nonenal. Our data suggest that edaravone may be clinically effective in the treatment of acoustic trauma, especially if given within 21 h of noise exposure.

Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig

The protective effect of dexamethasone (DEX) against noise-induced trauma, as reflected in hair cell destruction and elevation in auditory brainstem response (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump directly into scala tympani and, on the fourth day after pump implantation, exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control animals) and a similar attenuation of the noise-induced ABR threshold shifts, observed 7 days following exposure (significant at 100 ng/ml DEX animals compared to AP control animals). These physiological and morphological results indicate that direct infusion of DEX into the perilymphatic space has protective effects against noise-induced trauma in the guinea pig cochlea.

Cochlear Administration of Adenosine Triphosphate Facilitates Recovery from Acoustic Trauma (Temporary Threshold Shift)

Background: Adenosine triphosphate (ATP) has often been used in the treatment of acoustic trauma although evidence supporting its clinical use was lacking. The aim of this study was to evaluate the chronic effects of ATP on acoustic trauma in guinea pigs. Methods: We infused ATP into the perilymph of the guinea pig cochlea concurrently with intense noise exposure to investigate the effect of ATP on the process of recovery after acoustic trauma. We assessed auditory brainstem response (ABR) thresholds to evaluate cochlear function. Results: After noise exposure (120 dB SPL, 5 h), ABR thresholds showed an increase of approximately 50 dB SPL that returned to normal after 14 days. Cochlear function in ATP-treated ears recovered more quickly than in control ears. The effect of ATP was inhibited by the administration of the ATP receptor antagonist: pyridoxal- phosphate-6-azophenyl-2′,4′-disulfonic acid. Conclusion: These results suggest that ATP mitigates the effects of noise trauma through the ATP receptor.

Changes of Hair Cell Stereocilia and Threshold Shift after Acoustic Trauma in Guinea Pigs: Comparison between Inner and Outer Hair Cells

The vulnerability of inner hair cells (IHCs) and outer hair cells (OHCs) to acoustic overstimulation is still controversially discussed. The present study was undertaken to investigate the vulnerability of IHCs and OHCs and the relation between chronological changes of auditory threshold shifts and stereocilia damages on IHCs and OHCs in guinea pigs after moderate acoustic trauma, caused by a single continuous exposure to pink noise (20 Hz to 20 kHz) of around 106 ± 2 dB SPL for 44 h. Stereocilia changes and threshold shifts of auditory brainstem responses (ABR) were assessed at regular intervals after noise exposure for 9 weeks. Scanning electron microscopy demonstrated the morphological changes of steriocilia as early as 1 day after noise exposure. The morphological changes included fused, bent, collapsed, and even missing stereocilia. These damages were more prominent on IHCs than on OHCs. The shift of ABR threshold was not parallel to the chronological change of the stereocilia on IHCs as well as OHCs. The elevation of the ABR threshold (40–60 dB SPL) was greatest on the 1st day after noise exposure, whereas the stereocilia showed the most damage 7 days after noise exposure. Combined with the results from previous studies, we conclude that moderate-level (around 105–110 dB) noise tends to induce more damage to the stereocilia of IHCs than of OHCs. Other damage (e.g., metabolic disturbance) than morphological damage of hair cell stereocilia may contribute partially to the hearing threshold shift induced by moderate acoustic overstimulation.

Effects of silica on the outcome from experimental spinal cord injury: Implication of macrophages in secondary tissue damage

A model of spinal cord trauma in guinea-pigs, using lateral compression to a set thickness, produces a delayed functional loss at one to two days, followed by a partial recovery over several weeks, as measured using hindlimb motor behavior, vestibulospinal reflex testing, and mapping the receptive field of the cutaneous trunci muscle reflex. The role of inflammatory events in these secondary changes, was investigated with intraperitoneal injections of the macrophage toxin, silica. In one experiment, 11 matched pairs of animals were injured. One of each pair was selected randomly and injected with a suspension of 1.2 g of silica dust in sterile saline, immediately after injury and surgical closure. In a second experiment, involving 10 pairs of guinea-pigs, a similar dose of silica was administered to one of each pair at either one or two days before the injury. The animals survived up to three months, then were fixed by perfusion with glutaraldehyde. Histopathology of the lesion was quantified by line sampling of myelinated axons, and by measurement of blood vessels, in plastic sections through the center of the lesion. Surgery, injury, analysis of behavior and histology were all performed without knowledge of the experimental status of the animal. The secondary onset of functional loss below the lesion appeared to be delayed by one to two days in silica-treated animals with respect to controls. The number of myelinated axons at the center of the lesion, examined at two weeks to three months after injury was higher in the animals injected with silica immediately after surgery, most significantly in the dorsal quadrant of the cord. Myelin sheath thickness and axon caliber distribution were not different. Hypervascularity of the lesion was significantly reduced in animals injected with silica within one day of injury. These findings support the hypothesis that inflammatory activity plays an important role in secondary tissue damage, and that it may be responsible for some proportion of long-term neurological deficits, but do not suggest a prominent role for early macrophage activity in the mechanisms of demyelination.

Morphometric analysis of blood vessels in chronic experimental spinal cord injury: Hypervascularity and recovery of function

A model of spinal cord trauma in guinea pigs, based on compression to a set thickness, was described previously. Compression injuries of the lower thoracic cord were produced in 11 anesthetized, adult guinea pigs, and the outcome monitored, using successive behavioral tests and morphometry of the lesion at 2–3 months. This report describes changes in the vascularity of the spinal cord, based on light microscopic analysis of 1 μm plastic transverse sections through the center of the lesion. Mean blood vessel density in these lesions was approximately twice that found in equivalent regions of normal, uninjured spinal cords, and hypervascularity of the white matter extended at least four spinal cord segments cranially and caudally from the lesion center. Capillary diameter distribution was significantly shifted to larger values and large perivascular spaces surrounded most capillaries and pre- and post-capillary vessels. Extent of hypervascularity was not correlated with the overall severity of the injury, but there was a significant positive correlation between the density of blood vessels in the outer 400 μm of the white matter and secondary loss of neurological function below the lesion, seen between one day and eight weeks after injury. This suggests that hypervascularization of the lesion is related to secondary pathological mechanisms in spinal cord injury, possibly inflammatory responses, that are relatively independent of the primary mechanical injury but more closely connected with loss and recovery of function.

Morphometric analysis of a model of spinal cord injury in guinea pigs, with behavioral evidence of delayed secondary pathology

A model of spinal cord trauma in guinea pigs is described, based on the concept of compression to a set thickness, as an alternative to compression or contusion with a set force or displacement. The model is technically simple and reliable and circumvents some of the biomechanical problems of contusion techniques. It was designed initially to produce moderate injuries, allowing significant recovery of function. A pair of forceps was modified to form an instrument to compress the spinal cord laterally, over a 5-mm length, to a thickness of 1.2 mm. Such compression injuries of the lower thoracic cord were produced in 12 anesthetized, adult guinea pigs, and the outcome monitored, using successive behavioral tests and morphometry of the lesion at 2–3 months. Chronic histopathology was examined quantitatively with line-sampling of axons in 1-μm plastic sections through the lesion center, stained with toluidine blue. The type and distribution of damage to axons was similar to that seen following weight-drop contusion trauma in cats. Spinal cord function was examined by means of hindlimb reflex testing and motor behavior, vestibulospinal reflex testing, and mapping the receptive field of the cutaneus trunci muscle (CTM) reflex. These injuries characteristically resulted in a delayed onset of functional deficits at 1–2 days after injury, followed by partial recovery over the course of several weeks. Overall, functional outcome correlated significantly with the number of surviving axons in the lesion. The phenomenon of “secondary” pathology was striking at the behavioral level, whereas evidence of delayed injury has been indirect in most animal models. The onset of this secondary process occurred with a longer delay than has been assumed or implied by most suggested mechanisms of secondary pathology. The time course of secondary loss and recovery may be related to that of the inflammatory response at the injury site, particularly the phagocytic activity of macrophages.