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A pneumoperitoneum perpetuates severe damage to the ultrastructural integrity of parietal peritoneum in gastric perforation-induced peritonitis in rats.

BACKGROUND: Minimal invasive surgery is increasingly used in conditions complicated by peritonitis-e.g., peptic ulcer perforation. This study was devised to assess the effect of a pneumoperitoneum (PP) on the ultrastructural integrity of parietal peritoneum in perforation-induced peritonitis. METHODS: Anesthetized rats were subjected either to standardized gastrotomy simulating gastric perforation (groups Ia-d; IIa-d) or to sham perforation (groups IIIa-d, IVa-d). In group I (a-d) and III (a-d), CO2 was insufflated 12 h after gastrotomy for 60 min (Pia 4 mmHg). Glutaraldehyde was administered intraperitoneally at the end of the PP period while the abdominal wall was still extended (group index a), as well as 30 sec (b), 2 h (c), and 12 h (d) after desufflation. Specimens were taken from the parietal peritoneum of the left diaphragm for scanning electronic-microscopic (SEM) analysis. In groups II (a-d) and IV (a-d), simple puncture of the abdominal cavity was performed, and specimens were taken at corresponding times. RESULTS: In group Ia (gastric perforation with PP), distortion of the mesothelial cell layer with concomittant opening of stomata to the submesothelial tissue was already observed in specimens harvested while the abdominal wall was still extended. Concomitantly, scarce microvilli, which appeared coarse and thickened, were lying flat on top of the mesothelial cells. After desufflation (groups Ib-c), a rapid process of mesothelial disintegration with disruption from the submesothelial layer and vanishing of microvilli occurred. At 12 h after PP (group Id), complete deterioration of mesothelial cell integrity was observed. In groups IIa-c (gastric perforation without PP), microvilli appeared shrunk and coarse, while integrity of the mesothelial cell layer remained intact up to 2 h after the abdominal puncture. At 12 h after abdominal puncture (group IId), the microvilli had nearly completely vanished and the mesothelium was breaking apart into multiple soils. CONCLUSIONS: In SEM analysis of parietal peritoneum, premature distortion, and disintegration of the mesothelial cell layer was observed in animals exposed to increased abdominal pressure in addition to gastric perforation-induced peritonitis.

Animals↗

Treatment of endoscopic esophageal perforation.

BACKGROUND: The increasing usage of flexible endoscopy leads to a higher incidence of esophageal perforations, whose treatment strategies (conservative or operative) still are discussed controversially. We present our experiences and therapy concepts in relation to 75 iatrogenic esophageal perforations. PATIENTS: Between 1983 and 1997, 75 patients were treated for endoscopic perforation of the esophagus. The gender distribution was 31 females (41.3%) and 44 males (58.7%), with a mean age of 64.4 years (range 2-90 years). RESULTS: Therapeutic endoscopy was the most common cause of perforation (73 of 75 patients; 97.3%). Diagnostic endoscopy caused perforation in 2 patients (2.7%). The perforation was located in the cervical part of the esophagus in 7 patients (9.3%), the intrathoracic part in 25 patients (33.3%), and the abdominal part in 43 patients (57.3%). In this study population, 25 patients (33.3%) were treated surgically, and 50 patients (66.7%) conservatively. The overall in-hospital mortality rate was 14 of 75 patients (18.7%). In the surgically treated group the rate was 6 of 25 patients (24%) and in the conservative group 8 of 50 patients (16%). CONCLUSIONS: The decision of a treatment strategy depends on different factors such as the location and extent of the injury, the time interval between perforation and treatment onset, the preexisting diseases, and the patient's general condition. In view of these factors, an individual therapy concept should be determined for every patient.

Adolescent↗

Neonatal gastrointestinal perforations.

Neonatal gastrointestinal perforation has been associated with mortality rates of 40% to 70%. Over the past 20 years, 81 infants (46 boys and 35 girls) were treated for a gastrointestinal perforation at this institution. Perforation occurred from birth to 50 days (average, 8.2 days). Etiologies included necrotizing enterocolitis (NEC) (68%), meconium ileus (10%), and idiopathic gastric perforation (7%). Seventy-six infants underwent surgical exploration and five infants, considered too small or too sick to withstand a laparotomy, were treated with peritoneal lavage only. There were 29 deaths, an overall mortality of 36%. Ninety percent of the death occurred in patients with NEC, while all patients with gastric perforations survived. There has not been a significant improvement in survival in recent years, partly because of an increase in the proportion of NEC-related perforations. However, there is a narrowing of the mortality gap between low birth weight and normal weight infants. As the risk inherent to laparotomy in neonates is decreasing, other factors, such as the underlying etiology or the site of perforation, play a more important prognostic role.

Enterocolitis, Pseudomembranous↗

Tympanic membrane perforations in children.

We have assessed children with perforations of the pars-tensa presenting to an otolaryngology clinic over a 7-year period. We found that over 70% of the perforations followed the insertion of a ventilation tube. Using a novel method of dividing the tympanic membrane into quadrants, we were able to assess the sites and grade the size of perforations. The most common site of involvement, in all perforations, was the antero-inferior quadrant. With the exception of perforations following the use of T-tubes, we found little difference between the sites, sizes and hearing levels of ventilation tube and non-ventilation tube related perforations. Larger perforations resulted in a greater degree of hearing loss.

Child, Preschool↗

[Jejunal perforation by a fish bone diagnosed by CT-Scan: report of two cases].

The authors relate two cases of peritonitis secondary to jejunal perforation by a fish bone. Clinically, the first patient presented signs and symptoms of acute diverticulitis and the second had signs of duodenal perforation. In both cases, the diagnosis was made by the CT-scan revealing a linear radio-opaque object suggestive of a fish bone perforating the jejunum. At laparotomy of the first case, we found a perforation located above several loops of small bowel densely adhered to the nonabsorbable intra-abdominal mesh. Removal of the fish bone, suture of the jejunal perforation, washing and drainage of the abdominal cavity were performed. The mesh was removed and replaced by a polyglycolic acid mesh. In the second case, jejunal perforation occurred in an unaltered small bowel loop and a short intestinal resection was performed. The postoperative course was uneventful for both patients. These clinical cases allow us to discuss the several fish bone perforation site and our patients precipitating factors.

Aged↗

Colonoscopic perforations: a retrospective review.

Colonic perforation is no longer a rare complication of colonoscopy. Our previous report identified 45 such iatrogenic injuries from 1980 through 1994 (3082 colonoscopies per year). This follow-up of the ensuing 7 years examines changing trends of endoscopic usage in addition to management and prognosis of patients with colonoscopic perforations. Retrospective analysis of 78,702 colonoscopies (1994 through 2000, 11,243 colonoscopies per year) allowed assessment of medical records in all patients treated at our institution for colonic perforation. Sixty-six patients from our institution (perforation rate, 0.084%; 1 per 1192 procedures) and six patients from outside institutions were treated for colonic perforation following colonoscopy (41 women, 31 men; ages, 30-92 years; median, 73 years). Sixty-two patients underwent laparotomy, while 10 were managed nonoperatively. All 10 patients managed nonoperatively were void of peritoneal irritation by physical examination; eight patients did well (median hospital stay, 5.5 days; range, 0-12), but one death (family declined operative intervention) and one pelvic abscess requiring percutaneous drainage were noted. Peritoneal irritation by physical examination was evident in 57 of 62 patients undergoing laparotomy. Perforations occurred throughout the colon: right, 22 (31%); transverse, 5 (7%); left, 44 (61%); and unknown, 1 (1%). Thirty-eight patients (61%) underwent primary repair or resection with anastomosis. Fecal diversion was used in 100% of patients with extensive peritoneal contamination (n = 12) and 40% of patients with moderate contamination (12 of 30). Perioperative morbidity (39%) and mortality (8%) were significant. Factors predicting a poor outcome included delayed diagnosis, extensive peritoneal contamination, and patients using anticoagulants (P < .05). Compared with our prior study, the present review highlights a higher prevalence of injury based on more frequent use of colonoscopy. Perforation rates remain around 0.08%. While nonoperative management is viable in patients void of peritonitis, expedient surgical intervention seems to facilitate patient recovery.

Adult↗

Controlled trial of immediate endoluminal closure of colon perforations in a porcine model by use of a novel clip device (with videos).

BACKGROUND: Although endoluminal closure of a small perforation of the colon is technically feasible, the outcome of such a closure is unclear. OBJECTIVE: Our purpose was to evaluate the feasibility and the outcome of endoluminal closure of a small perforation of the colon with a novel clip device, the InScope MultiClip Applier (IMCA), and to assess the number of clips required for successful closure. DESIGN: Prospective controlled study. SETTING: University hospital. ANIMALS: 17 pigs. INTERVENTIONS: A 2-cm full-thickness colon perforation was randomized to 3 groups: control, no closure (n = 4), 2-clip closure (n = 7), and 4-clip closure (n = 6). MAIN OUTCOME MEASUREMENTS: (1) Technical feasibility of closure, (2) closure time, (3) clinical monitoring for 2 weeks, (4) necropsy (day 14), and (5) healing by a dye leak test and histologic examination. RESULTS: Endoscopic closure of the colon perforation was technically successful in 12 of 13 animals. A wide gaping hole prevented satisfactory closure in 1 animal. The median time for closure with 2 and 4 clips was 2 and 3 minutes, respectively. Clip closure of perforation prevented clinical sepsis (P = .008) and diminished the risk for fibrinous peritonitis (P = .02 for a single test of hypothesis; however, correction for the multiple testing of data removes this significance) and adhesion formation (P = .008) compared with controls, without any leakage. The outcomes of 2- and 4-clip closure were similar. CONCLUSIONS: Endoluminal closure of a 2-cm colon perforation with clips is successful in preventing peritonitis and adhesions and it can be accomplished quickly with this novel device. Clip closure at 1-cm intervals is sufficient for successful closure of a 2-cm colon perforation.

Animals↗

Mediolateral graft tympanoplasty for anterior or subtotal tympanic membrane perforation.

OBJECTIVE: To describe and evaluate the mediolateral graft tympanoplasty for the reconstruction of anterior or subtotal tympanic membrane (TM) perforation. STUDY DESIGN AND SETTING: Retrospective study of 100 patients who underwent the mediolateral graft tympanoplasty at community and tertiary care centers from 1995 to 2001. All patients underwent preoperative and postoperative audiograms. Posterior tympanomeatal flap is elevated same as in the medial (underlay) graft tympanoplasty. Anterior-medial canal skin is elevated down to the annulus. At the annulus, only squamous epithelial layer of TM is elevated up to anterior half of the TM perforation. Temporalis fascia is grafted medial (underlay) to the posterior half of the perforation and lateral (overlay) to the anterior half of the de-epithelialized TM perforation, up to the annulus. Anterior canal skin is rotated to cover the fascia graft and TM perforation as a second-layer closure. Patients were followed for at least 6 months. Outcome was considered successful if the TM is intact. RESULTS: There were 3 failures (97% success rate), attributable to a postoperative infection, anterior blunting, and recurrent cholesteatoma, respectively. There was no significant postoperative hearing loss compared with preoperative hearing. More than 70% of the operated ears had hearing improvement of 0-40 dB (0-10 dB in 19% of ears, 11-20 dB in 44%, 21-30 dB in 7%, and 31-40 dB in 4%) even without ossiculoplasty. With ossiculoplasty using either partial ossicular replacement prosthesis (PORP, 15%) or total ossicular replacement prosthesis (TORP, 11%), there were various degree of hearing improvement from 11 to 30 dB. CONCLUSION AND SIGNIFICANCE: The mediolateral graft method is superior to the traditional medial or lateral graft technique for the reconstruction of large anterior or subtotal TM perforation. This new method should help otologic surgeons to improve outcome of tympanoplasty for anterior or total TM perforation. EBM RATING: C-1.

Audiometry, Pure-Tone↗

Acute diverticulitis with colon perforation in renal transplantation.

INTRODUCTION: Acute diverticulitis with colon perforation is a serious condition in transplant recipients. The aim of this study was to analyze our experience with colon perforations among 875 renal transplant recipients between January 1986 and September 2004. METHODS: Patients were analyzed by age, gender, steroid dosage, time interval from the transplantation, delay between symptoms and surgery, clinical presentation, surgical procedure, graft and patient outcomes. RESULTS: We identified 8 patients with colon perforation. The incidence of perforation was 0.9%. Mean age at the the time of perforation was 58.5 years. Fever, abdominal pain, localized or diffuse signs of peritonitis, and leukocytosis were present in 7 patients (87.5%). Three patients (37.5%) were on steroid-free immunosuppression, whereas in 2 cases (25%) the steroid dosage was >20 mg/d. The mean interval between transplantation and perforation was 4.1 years. Two episodes (25%) occurred within 1 month following transplantation and the other 6 (75%) between 1 and 15 years. The interval between the onset of symptoms and surgery was longer than 48 hours in 1 patient (12.5%). In 5 cases (62.5%), a Hartmann procedure was performed; in 2 patients (25%), a resection with primary anastomosis was preferred. The last patient had a direct suture of the colon. Mortality rate was 12.5%. At a median follow-up of 6.1 years, 6 patients (75%) are alive with 5 functioning grafts. CONCLUSIONS: Colon perforations in renal transplant recipients remain a challenging surgical problem. An aggressive diagnostic attitude and an immediate surgical treatment may contribute to significantly decrease the incidence and the mortality of this complication.

Colonic Diseases↗

Emergency operations for nondiverticular perforation of the left colon.

OBJECTIVE: Although diverticulitis is the most common cause of large bowel perforation, other disease may result in left colonic peritonitis. The aim of this study was to evaluate and compare the incidence, management, and outcome of patients with different causes of nondiverticular left colonic perforations. PATIENTS AND METHODS: From January 1992 to September 2000, 212 surgical patients underwent emergency operation for distal colonic peritonitis. Perforations were caused by diverticulitis in 133 patients (63%) and by a nondiverticular process in 79 (37%). Mortality and morbidity in patients with nondiverticular perforation of the distal large bowel its relationship with the general conditions, the grade and the cause of peritonitis were analysed. Four types of surgical procedures were used. Hartmann's procedure was performed in 40 patients (51%); intraoperative colonic lavage, resection, and primary anastomosis (ICL) in 27 patients (34%); colostomy in 7 (9%); and subtotal colectomy in 5 (6%). RESULTS: Perforated neoplasm, the most common cause of peritonitis, was observed in 30 patients, colonic ischemia in 20, iatrogenia in 13, and other causes in 16 patients. One or more complications were observed in 57 patients (72%); among causes of perforation, colonic ischemia was significantly associated with the longest hospital stay and highest mortality. Eighteen patients (23%) died. CONCLUSIONS: Left large bowel perforation by nondiverticular disease is associated with high mortality and morbidity. The prognosis of patients is determined by the development of septic shock and colonic ischemia, as underlying disease, may influence patient survival.

Adult↗

Gastrointestinal perforation in infants.

We found that the mortality rate was no greater in patients with necrotizing enterocolitis complicated by perforation compared with the rate in those with other causes of perforation in similar weight classes. Iatrogenic injuries had a 50 percent mortality rate in all gestational age and birth weight categories and, therefore, great caution and surveillance are of utmost importance when using invasive monitoring and therapeutic modalities to prevent this cause of perforation. Term infants had a preponderance of mechanical causes of perforation which mainly occurred in the foregut and proximal midgut, whereas premature infants have a preponderance of asphyxial or ischemic events underlying perforations which mainly occurred in the ileocolic region and were often associated with necrotizing enterocolitis. Although neonatal intestinal perforation is a catastrophic event, the very premature infant weighing less than 1,000 g at birth is at significantly greatest risk. The discouraging 20 percent survival rate in the less than 1,000 g premature infants presents a challenge to the surgeon, since the overall survival rate was 59 percent and the term infants had a 78 percent survival rate. A substantial share of the mortality in the infants weighing less than 1,000 g at birth relates to the occurrence of intracerebral hemorrhage and bronchopulmonary dysplasia. Vigorous medical and surgical approaches can be used to salvage premature infants in all weight classes with gastrointestinal perforation.

Enterocolitis, Pseudomembranous↗

Clinical presentation and management of iatrogenic colon perforations.

BACKGROUND: Because iatrogenic colonic perforation is uncommon, surgical management of this complication has been based on the civilian trauma experience. In this study, we determine the incidence, clinical presentation, and management of colonic perforations resulting from colonoscopy or barium enema. PATIENTS AND METHODS: The medical records of all patients with colorectal perforations due to barium enema or colonoscopy seen over a 5-year period were reviewed. RESULTS: Twenty-one patients, 12 males and 9 females aged 66 +/- 16 years, undergoing evaluation for polyps and bleeding (11), diverticulosis (4), diarrhea (2), or miscellaneous indications (4) sustained colonic perforation from colonoscopy (18; 0.20%) or barium enema (3; 0.10%). Abdominal pain, 66% (13), and fever, 24% (5), were the most frequent symptoms encountered and extraluminal air, 67% (14), the most common radiologic finding. The site of perforation was the rectosigmoid in 62% (13) of patients. Eighteen patients underwent surgery; 11 within 24 hours (group I) and 7 patients within 6.0 +/- 4 days (group II). Fifty percent (9 of 18) had primary repair or resection with anastomosis without mortality. Of the 6 patients initially treated nonoperatively, 3 subsequently underwent surgery. Both deaths, one in group I and one in group II, occurred in patients who had colonic diversion for perforation following colonoscopy. CONCLUSION: We conclude that in the absence of significant contamination either primary repair or resection and anastomosis can be performed with acceptable morbidity for iatrogenic perforations of the colon.

Adolescent↗

Instrumental perforation of the esophagus in benign disease.

Over a period of seven years, a total of 1,831 endoscopic procedures were performed in patients with benign esophageal disease. These comprised flexible esophagoscopy (848), flexible esophagoscopy and dilation (924), pneumatic dilation (29), and rigid esophagoscopy (30). There were 14 episodes of perforation: 1 was cervical, 2 were abdominal, and 11 were perforations of the intrathoracic esophagus (7 occurred at or immediately above a stricture). The diagnosis was made immediately in 9 and within six hours in all but 1 patient. Treatment was emergency surgery in 12 patients, 2 of whom died. The major cause of death was respiratory failure. The overall incidence of perforation was 0.76%. The incidence of perforation was 0.35% (3/848) for flexible esophagoscopy alone, 0.38% (3/792) for dilation with Maloney mercury-weighted bougies, and 3.8% (5/132) for dilation with other bougies. Our experience indicates that instrumental perforation in benign esophageal disease carries a considerable mortality rate in spite of prompt recognition and surgical treatment. Successful dilation with mercury-weighted bougies can be achieved in 86% of benign strictures with an incidence of perforation similar to that for flexible esophagoscopy alone. Difficult strictures and the use of other bougies are associated with a tenfold higher incidence of perforation.

Aged↗

Esophageal perforation: an increasing challenge.

Esophageal perforation continues to be a challenge. The overall incidence is rising even though iatrogenic perforations are decreasing. With early diagnosis followed by prompt surgical treatment, most patients can be expected to survive. Roentgenographic contrast studies demonstrated a perforation in all but 1 of our patients who had this examination and should be used early in patients suspected of having an esophageal perforation. The mortality rate is directly related to the interval between perforation and initiation of treatment. Nonoperative treatment, even for cervical esophageal perforations, is not advocated. An aggressive approach, consisting of closure of the perforation and adequate drainage, is indicated for both diagnosis and surgical treatment.

Abdomen↗

Idiopathic intestinal perforations in the newborn: an increasingly common entity.

Between 1982 and 1987 seven neonates ranging in age from 24 hours to 1 week were treated for idiopathic intestinal perforations at the Montefiore Medical Center, Albert Einstein College of Medicine. Four of the infants were born prematurely; three were full term. Five were being treated in an intensive care nursery when the perforation was diagnosed. All infants whose perforations were due to necrotizing enterocolitis, appendicitis, Hirschsprung's disease, meconium ileus, intestinal atresias, or drug therapy are excluded from the series. None of the infants had associated anomalies. The sites of the perforations were as follows: two in the jejunum, two in the ileum, one in the cecum, and two in the transverse colon. Six of the perforations were on the antimesenteric aspect of the bowel; one was on the mesenteric aspect. The sizes of the perforations ranged from pinhole to 1 cm in diameter. All the infants did well. Pathologic examination of the resected specimens failed to reveal an etiology for the perforations. There were no cases of duplication or muscular hypoplasia. We believe the etiology of this condition may be ischemic necrosis, secondary to a localized vascular accident in the wall of the affected viscus, but we do not have a good explanation for the upsurge in cases we are seeing.

Colonic Diseases↗

Repair of chronic tympanic membrane perforations with fibroblast growth factor.

A number of angiogenic growth factors have been shown to accelerate wound healing. Previous work has demonstrated that topical application of epidermal growth factor is effective in healing chronic tympanic membrane perforations in an animal model. Theoretically, fibroblast growth factor may result in a superior healed membrane through preferential stimulation of the fibroblasts within the middle layer of the tympanic membrane. To test this hypothesis, the effects of exogenously applied fibroblast growth factor on the chronically perforated tympanic membrane were evaluated. A buffered solution of fibroblast growth factor (25 microliters of fibroblast growth factor, 0.2 mg/ml) was administered to a Gelfoam pledget placed over chronic tympanic membrane perforations in chinchillas. Control ears were treated with Gelfoam and the buffer solution only. Complete closure of the tympanic membrane perforation was observed in 81% (13 of 16) of the fibroblast growth factor-treated ears, but in only 41% (7 of 17) of the controls (p = 0.05). Heading took place gradually, requiring an average of 4 weeks for the fibroblast growth factor-treated and 6.5 weeks for the control ears that healed. The relatively high healing rate for the control group does not imply that the pretreatment perforations were not chronic, rather there appears to be some efficacy to the control protocol of repeated applications of Gelfoam and buffer. A histologic analysis of the fibroblast growth factor-healed eardrums immediately after closure demonstrated hypertrophy of the squamous and fibrous layers of the tympanic membrane. Over time, the eardrum thinned to reach proportions similar to those of the normal tympanic membrane, including the presence of a substantial middle fibrous layer. A screening ototoxicity study revealed no structural damage to the organ of Corti after growth factor treatment. To assess the potential for systemic toxicity, blood and peripheral tissues were analyzed for radioactivity at time points during a 48-hour period after application of 25 microliters of 125I-fibroblast growth factor to the perforated tympanic membrane. More than 78% of the radioactivity remained at the application site. Given the tiny original dosage, the small fraction absorbed systemically is minuscule and highly unlikely to induce adverse effects in light of published toxicity data. On the basis of these promising safety and efficacy data in the chinchilla model, clinical trials of fibroblast growth factor in repair of chronic tympanic membrane perforations in human beings are being initiated.

Administration, Topical↗

Eardrum perforation in explosion survivors: is it a marker of pulmonary blast injury?

STUDY OBJECTIVES: To determine whether isolated eardrum perforation is a marker for concealed blast lung injury in survivors of terrorist bombings. METHODS: Survivors who arrived at hospitals after 11 terrorist bombings in Israel between April 6, 1994, and March 4, 1996, were examined otoscopically by ear, nose, and throat specialists. All patients with eardrum perforation underwent chest radiography and were hospitalized for at least 24 hours for observation. The clinical course and final outcome of patients with isolated perforation of the eardrums and of those with other blast injuries were surveyed. RESULTS: A total of 647 survivors were examined; 193 (29.8%) of them sustained primary blast injuries, including 142 with isolated eardrum perforation and 51 with other forms of blast injuries (18 with isolated pulmonary blast injury, 31 with combined otic and pulmonary injuries, and 2 with intestinal blast injury). Blast lung injury was promptly diagnosed on admission by physical examination and chest radiography. No patient presenting with isolated eardrum perforation developed later signs of pulmonary or intestinal blast injury (mean 0%; 95% confidence interval, 0% to 2.7%). CONCLUSION: Isolated eardrum perforation in survivors of explosions does not appear to be a marker of concealed pulmonary blast injury nor of a poor prognosis. Therefore, in a mass casualty event, persons who have sustained isolated eardrum perforation from explosions may safely be discharged from the emergency department after chest radiography and a brief observation period.

Adolescent↗

Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata.

Transection of the entorhino-dentate perforant path is a well known model for lesion-induced axonal sprouting and glial reactions in the rat. In this study, we have characterized the microglial reaction in the dentate molecular layer of the SJL/J and C57Bl/6 mouse. The morphological transformation of the microglial cells and their densitometrically measured Mac-1 immunoreactivity were correlated with the density of silver-impregnated axonal and terminal degeneration and the myelination of the degenerating medial and lateral perforant pathways. Anterograde axonal and terminal degeneration leads to: (i) altered myelin basic protein immunoreactivity with the appearance of discrete myelin deposits preferentially in the denervated medial and significantly less so in the lateral perforant path zone from day 2 after lesioning; (ii) an increase in number and Mac-1 immunoreactivity of morphologically-changed microglial cells in the denervated perforant path zones with more pronounced morphological transformation of microglia in the medial than in the lateral perforant path zones at day 2 but not day 5 after lesioning; and (iii) a linear correlation between the density of microglial Mac-1 reactivity and axonal degeneration in the medial but not in the lateral perforant path zone at two days postlesion, and a linear correlation in both zones at five days postlesion. We propose that the differentiated microglial response is due to the different densities of axonal and terminal degeneration, as observed in the individual cases. The finding of a potentiated or accelerated microglial activation in the medial as compared to the lateral perforant path zone suggests different kinetics of microglial activation in areas with degenerating myelinated and unmyelinated fibers.

Animals↗